Canadian clinical trial registry

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Information is also accessible through the patient and families tab. Family friendly summaries are created and reviewed by our advocacy partners. The information is updated to the best of our knowledge but might not reflect the latest information. Note that most studies are only available at a limited number of sites, please click on ‘further information’ for details. Studies, particularly early phase trials, may also temporarily close to enrolment or not have slots available for all treatment groups. In all cases, study teams at individual C17 centres will have the most up-to-date information.

86 results found

Title
Status

 

YmAbs201 - A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

Open

YmAbs201 - A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

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DiagnosisNeuroblastomaStudy StatusOpen
PhaseII
AgeChild, Adult, Older Adult - (1 Year and older)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment Administrationnaxitamab (intravenous); GM-CSF (sub-cutaneous)
Last Posted Update2024-01-19
ClinicalTrials.gov #NCT03363373
International Sponsor
Y-mAbs Therapeutics
Principal Investigators for Canadian Sites
The Hospital for Sick Children – Dr. Daniel Morgenstern
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

 

 

Study Description

Brief Summary:

Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose.

Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2

Detailed Description:

Each patient will receive treatment for up to 101 weeks following the first Naxitamab administration. After the end of trial visit, each patient will enter a long-term follow-up where they will be monitored for up to 5 years after first treatment cycle.

Each investigational cycle is started with 5 days, days -4 to 0, of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5, totalling 9 mg/kg per cycle.

Treatment cycles are repeated every 4 weeks (±1 week) until complete response or partial response followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. End of treatment will take place around 8 weeks after the last cycle and thereafter long-term follow-up will continue.

Inclusion Criteria
  • Diagnosis of neuroblastoma as defined per International Neuroblastoma Response Criteria
  • High-risk neuroblastoma patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including stable disease, minor response and partial response) evaluable in bone and/or bone marrow.
  • Life expectancy ≥ 6 months
Exclusion Criteria
  • Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks before 1st dose of GM-CSF
  • Evaluable neuroblastoma outside bone and bone marrow
  • Existing major organ dysfunction > Grade 2, with the exception of hearing loss, hematological status, kidney and liver function
  • Active life-threatening infection

STEP-RB - Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma

Closed to enrollment

STEP-RB - Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma

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DiagnosisRetinoblastoma Study StatusClosed to enrollment
PhaseI
AgeChild - (up to 17 Years)RandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationTopotecan - administered using an episcleral plaque (chemoplaque), an implant which contains topotecan (drug). The implant is attached to the outside of the eye and delivers topotecan directly into the eye.
Last Posted Update2024-01-09
ClinicalTrials.gov #NCT04428879
International Sponsor
The Hospital for Sick Children
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Daniel Morgenstern
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

 

 

Study Description

Brief Summary:

This single site, single-arm, non-randomized, dose escalation phase I toxicity clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan in patients with active residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy.

Detailed Description:

Retinoblastoma is the most common pediatric malignant intraocular tumour and originates from the retina. Treatment of eyes with advanced intraocular retinoblastoma remains a challenge. The historic standard of care for patients with unilateral disease is enucleation and for those with bilateral disease, a variety of modalities have been tried. These include radiation therapy, systemic chemotherapy, periocular administration of chemotherapy, selective intra-arterial chemotherapy, and intravitreal chemotherapy. Unfortunately, all of these modalities are associated with significant morbidity and investigators are looking for new ways to treat these patients either with novel directed drug delivery methods or with new less toxic agents. This study will evaluate the safety and efficacy of topotecan delivered directly to the eye using a novel sustained-release topotecan episcleral plaque (also referred to as a Chemoplaque) in patients with active residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy. The study intervention involves the insertion and removal of the Chemoplaque, examinations under anaesthesia (EUAs), visits to clinic to monitor for adverse events throughout, and post plaque removal toxicity evaluation. EUAs, clinic visits and laboratory tests are standard of care for retinoblastoma patients.

Inclusion Criteria
  1. Age. Participants must be <18 years of age.
  2. Diagnosis and Treatment. Participants must have: (i) active residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy (chemotherapy, systemic or intra-arterial, focal therapy or brachytherapy) or (ii) unilateral Group D retinoblastoma at diagnosis with no previous treatment.
  3. One eye will be the Study Eye. When participants have two eyes with retinoblastoma, the eye with worst disease or best vision potential will be designated the Study Eye. There will only be one eye per child treated in this Phase I study, since treatment of two eyes would double the systemic dose of drug. The Non-study eye will be treated by standard of care, with only focal therapy during the Study Period, if required.
  4. Disease status. Study eye must have vision potential and no clinical features suggestive of high risk of extraocular extension.
  5. Performance status. Lansky play score ≥ 50 if <16 years of age; Karnofsky performance scale of ≥ 50 if ≥16 years of age (Appendix I)
  6. Organ function:

    1. Adequate bone marrow function and platelet count
    2. Adequate renal function
    3. Adequate liver function
  7. Pregnancy prevention. Females of reproductive potential must agree to the use of highly effective contraception during study participation and for an additional 40 days after the end of the Chemoplaque administration
  8. Informed consent. All participants and/or their parents or legally authorized representatives must have the ability to understand and the willingness to sign a written informed consent. Assent, where appropriate, will also be obtained.
Exclusion Criteria
  1. Disease status. Participants known to have any of the following:

    1. tumour involving the optic nerve rim
    2. clinical or EUA evidence of extraocular extension
    3. evidence of metastatic retinoblastoma
    4. existing neuroimaging showing suspicion of, or definitive, optic nerve invasion, trilateral retinoblastoma or extra-ocular extension.
  2. Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives thereof.
  3. Concomitant treatment. Participants may not receive chemotherapy or other focal retinoblastoma therapy or any other investigational agent within 3 weeks of the placement and removal of the Chemoplaque, nor while the Chemoplaque is in situ.
  4. Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent illness that, in the investigator's opinion, would put the participant at undue risk or limit compliance with the study requirements.
  5. Febrile illness. Participants with clinically significant febrile illness (as determined by the investigator) within one week prior to initiation of protocol therapy.
  6. Pregnancy and lactation. Females of reproductive potential must have a negative serum pregnancy test within 72 hours prior to initiation of protocol therapy. Due to the unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with the study agents, breastfeeding must be discontinued if the mother is treated on study.
  7. Compliance. Any condition of diagnosis that could in the opinion of the Principal Investigator or delegate interfere with the participant's ability to comply with the study instruction, might confound the interpretation of the study results, or put the participant at risk.

ACT15378 ISAKIDS - Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse

Suspended

ACT15378 ISAKIDS - Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse

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DiagnosisAcute Lymphoblastic Leukemia, Acute Myeloid LeukemiaStudy StatusSuspended
PhaseII
AgeChild - (up to 17 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationIntravenous for isatuximab; Other drugs as usually administered for leukemia therapy
Last Posted Update2024-01-08
ClinicalTrials.gov #NCT03860844
International Sponsor
Sanofi
Principal Investigators for Canadian Sites
Montreal Children’s Hospital - Dr. Surabhi Rawal
BC Children's Hospital - Dr. Amanda Li
Centres
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

 

 

Study Description

Brief Summary:

Primary Objective:

To evaluate the anti-leukemic activity of isatuximab in combination with standard chemotherapies in pediatric participants of ages 28 days to less than 18 years with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML)

Secondary Objectives:

  • Safety and tolerability assessments
  • Assessment of infusion reactions (IRs)
  • Pharmacokinetics (PK) of isatuximab
  • Minimal residual disease
  • Overall response rate
  • Overall survival
  • Event free survival
  • Duration of response
  • Relationship between clinical effects and CD38 receptor density and occupancy

Detailed Description:

The study will include a screening period of up to 21 days (Day -21 to -1), a study treatment period [Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute Myeloid Leukemia (AML)], a recovery period (until an end of treatment visit [within 30 days after hematological recovery]) and a follow-up period (until final analysis cut off date).

Inclusion Criteria
  • Participant must be 28 days to less than 18 years of age, at the time of signing the informed consent.
  • Participants must have a confirmed diagnosis of relapsed Acute Lymphoblastic Leukemia (ALL) of T- or B-cell origin including T-lymphoblastic lymphoma (LBL), or relapsed Acute Myeloblastic Leukemia (AML) including participants with history of myelodysplasia.
  • Participants must be previously treated for their disease and have relapsed or are refractory to most recent treatment. Participants in first or second relapse will be eligible regardless of the remission duration.
  • Participants with no more than 1 prior salvage therapy.
  • WBC counts below 20 x109/L on Day 1 before isatuximab administration
Exclusion Criteria
  • Any serious active disease or co-morbid condition which, in the opinion of the Investigator, may interfere with the safety of the study treatment or the compliance with the study protocol.
  • Participants must have been off prior treatment with immunotherapy/investigational agents and chemotherapy for >2 weeks and must have recovered from acute toxicity before the first study treatment administration. Treatment may start earlier if necessitated by the patient's medical condition (eg, rapidly progressive disease) following discussion with the Sponsor.
  • Prior stem cell transplant within 3 months and/or evidence of active systemic Graft versus Host Disease (GVHD) and/or immunosuppressive therapy for GVHD within 1 week before the first study treatment administration.
  • Participants with LBL with bone marrow blasts <5%.
  • Participants with Burkitt-type ALL.
  • Acute leukemia with testicular or central nerve system involvement alone.
  • Participants who have developed therapy related acute leukemia.
  • Live vaccine(s) within 30 days prior to the first IMP administration or plans to receive such vaccines during the study until 90 days after the last IMP administration.
  • Participants with white blood cell count > 50 x109/L at the time of screening visit.
  • Participants who have been exposed to anti-CD38 therapies within 6 months prior to Day-1.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

OZM-063 - A Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children With Unresectable or Progressive Low Grade Glioma (LGG)

Closed to enrollment

OZM-063 - A Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children With Unresectable or Progressive Low Grade Glioma (LGG)

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DiagnosisLow Grade GliomaStudy StatusClosed to enrollment
PhaseII
AgeChild, Adult - (6 Months to 18 Years)RandomisationYES
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment Administrationintravenous
Last Posted Update2024-01-08
ClinicalTrials.gov #NCT02840409
International Sponsor
The Hospital for Sick Children / Hoffmann-La Roche
Principal Investigators for Canadian Sites
Montreal Children’s Hospital – Dr. Geneviève Legault
The Hospital for Sick Children – Dr. Uri Tabori
Alberta Children’s – Dr. Lucie Lafay-Cousin
BC Children’s Hospital – Dr. Juliette Hukin
CHU Ste-Justine – Dr. Yvan Samson
Stollery Children’s Hospital – Dr. Bev Wilson
CHU de Quebec - Dr. Valerie Larouche
CancerCare Manitoba - Dr. Issai Vanan
Children’s Hospital of Eastern Ontario (CHEO) - Dr. Donna L. Johnston
Hamilton Health Sciences Centre - Dr. Uma Athale
Centres
Medical contact
Dr. Victor Lewis

 

Social worker/patient navigator contact
Wendy Pelletier
Clinical research contact
Debra Rich
Medical contact
Dr. Sarah McKillop
Dr. Sunil Desai

 

 

Social worker/patient navigator contact
Danielle Sikora
 Michelle Woytiuk 
Jaime Hobbs
Clinical research contact
Amanda Perreault
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Dr. Magimairajan Vanan
Social worker/patient navigator contact
Rhéanne Bisson
 
Clinical research contact
Rebekah Hiebert
Megan Ridler
Kathy Hjalmarsson

 

 

Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Dr. Henrique Bittencourt
Dr. Monia Marzouki
Dr. Sebastien Perreault (neuro-onc)
 
Social worker/patient navigator contact
Marie-Claude Charrette
 
Clinical research contact
Marie Saint-Jacques
 
Medical contact
Dr. Donna Johnston
Dr. Lesleigh Abbott
Dr. Doaa Abdel Fattah
 
Social worker/patient navigator contact
Sherley Telisma
 
Clinical research contact
Carol Duchenne
 
Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 

 

 

Study Description

This is an open-label, randomized, multi-center, comparator Phase II trial looking at the addition of Bevacizumab to Vinblastine in chemotherapy naïve pediatric patients with progressive Low Grade Glioma aged 6 months to less than18 years of age at the time of initiation of therapy. Participants will be randomized to Arm A or Arm B. Arm A includes 68 weeks of single agent Vinblastine administered once weekly IV. Arm B includes 68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks. Randomization will take place at the time of registration taking into account NF1 and BRAF-KIAA1549-fusion status.

Inclusion Criteria
  1. Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma 
  2. All patients must submit tumour tissue (fresh tumour tissue is recommended) and have pathological confirmation of LGG and determination of BRAF characteristics from the Hospital for Sick Children. Exceptions will be made for patients with neurofibromatosis type 1 who have not previously had a biopsy. NF1 patients are eligible without tissue confirmation but must have definitive clinical or radiographic evidence of tumour progression or risk for significant neurologic deterioration requiring immediate therapy. If a tissue sample for NF1 patients is available from a previous biopsy, it is required to be submitted for Central Review at the Hospital for Sick Children. Please refer to the lab manual for further details.
  3. Patients must have progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (< 95% or > 1.0 cm2 residual tumour) with necessity to begin treatment because of a risk of neurological impairment with progression.
  4. All patients on study must have measurable tumour (>1.0 cm2 of residual tissue if resection has been performed) within 28 days of enrollment.
  5. Patients must have received no prior therapy including chemotherapy, biological modifiers and/or radiation treatment for the tumour with the exception of surgery.
  6. Patient is able to start treatment within 14 working days after randomization.
  7. Post pubertal teenagers who are sexually active agree to use two methods of contraception during the treatment period and for at least 6 months after the last dose of study drug. Please refer to Appendix V for a list of acceptable methods of contraception.
  8. Lansky performance status > 50% for patients < 16 years of age. Karnofsky performance status > 50% for patients ≥ 16 years of age.
  9. Patients with neurologic deficits must have deficits that are stable for a minimum of 1 week prior to enrollment.
  10. Patients receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment.
  11. Life expectancy > 2 months at the time of enrollment.
  12. Parents/guardians must provide written informed consent and to agree that they (and the patient) will comply with the study protocol.
  13. Written assent by patient according to institutional guidelines.
  14. Patients must have adequate bone marrow function within 2 weeks prior to enrollment:

    • Hemoglobin ≥ 10 g/dL (may be supported )
    • Neutrophil count ≥ 1.0 × 109/L
    • Platelet count ≥ 100 × 109/L (transfusion independent)
  15. Patients not on a therapeutic dose of an anti-coagulant must have an INR ≤ 1.5 and an aPTT ≤ 1.5x institutional ULN for age within 2 weeks prior to enrollment. Anti-coagulation is permitted prior to enrollment on the condition that the patient is, according to the local clinical practice guidelines or approved product labeling, adequately anti-coagulated prior to enrollment.
  16. Patients must have satisfactory liver function within 2 weeks prior to enrollment:

    • AST ≤ 3x institutional ULN for age
    • ALT ≤ 3x institutional ULN for age
    • Total Bilirubin ≤ 1.5x institutional ULN for age
  17. Patients must have satisfactory renal parameters and meet the following criteria within 2 weeks prior to enrollment :

    • Serum creatinine must be ≤ 1.5x ULN for age. If the serum creatinine is > 1.5 × ULN, the glomerular filtration rate (either estimated or formal) must be >90 mL/min/1.73 m2, for patient to be enrolled.
    • Absence of clinically significant proteinuria, as defined by screening of the early morning urine (urine protein < 1g/L and/or albumin/creatinine ratio < 1.0 (mg/mmol)). If urine protein ≥ 1g/L, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment. Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 g. UPC ratio is calculated using one of the following formulas:

[urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL or [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L

Quality of Life Correlative Study Inclusion Criteria (Optional):

  1. Age ≥ 3 and < 18 years.
  2. English- or Spanish-speaking.
  3. No known history of a significant neurodevelopmental disorder prior to diagnosis of LGG (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation). Patients with NF1 are not excluded.
  4. No significant motor or sensory impairment that would prevent computer use and perception of the visual and auditory test stimuli.
Exclusion Criteria
  1. Children under 6 months of age.
  2. Pregnant or lactating females.
  3. Use of any investigational agent, systemic, targeted or immunotherapy prior to the first dose of study treatment.
  4. Any bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation).
  5. Patients with evidence of new symptomatic CNS hemorrhage (> grade I) on baseline MRI.
  6. Any significant cardiovascular disease, e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis, CVAs, transient ischemic attacks (TIAs), and systemic hypertension (i.e., a systolic and diastolic BP ≥ 95th percentile for age, sex), prior history of hypertensive crisis or hypertensive encephalopathy or stroke, uncontrolled cardiac arrhythmia within 6 months prior to enrollment .
  7. Any previous venous thromboembolism Grade 3 or higher (NCI CTCAE v. 4.03).
  8. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
  9. Unresolved infection.
  10. An active peptic or duodenal ulcer.
  11. Major surgical procedure (see Table 3 section 6.1.7), brain surgery, open biopsy or significant traumatic injury within 28 days prior to enrollment or the anticipation of the need for major (elective) surgery during the course of the study treatment.
  12. Intermediate surgical procedure (see Table 3 section 6.1.7) within 2 weeks of enrollment.
  13. Minor surgical procedures (see Table 3 section 6.1.7) within 3 days prior to the start of treatment (including the placement of a central line, including PICC line). Insertion of a port-a-cath will require a 7-day interval prior to the start of treatment.
  14. Non-healing surgical wound.
  15. A bone fracture that has not satisfactorily healed.
  16. Concomitant use of the following:

    • Aspirin (> 325mg/day) within 10 days of enrollment
    • Clopidogrel (> 75mg/day) within 10 days of enrollment
    • Use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes with INR and aPTT outside therapeutic standards according to institutional guidelines within 10 days of first dose of Bevacizumab. Note: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of the Baseline Visit. Prophylactic use of anticoagulants is allowed.
  17. Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.

LOXO-TRK-15003 (SCOUT) - A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

Closed to enrollment

LOXO-TRK-15003 (SCOUT) - A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

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DiagnosisSolid tumors with NTRK fusion, Brain Tumors with NTRK, Fusion infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast cancer Study StatusClosed to enrollment
PhaseI/II
AgeChild, Adult - (up to 21 Years)RandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationOral (capsule or in liquid form)
Last Posted Update2024-01-08
ClinicalTrials.gov #NCT02637687
International Sponsor
Bayer
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Daniel Morgenstern
CHU Ste Justine - Dr. Sébastien Perreault
BC Children's Hospital - Dr. Rebecca Deyell
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Dr. Henrique Bittencourt
Dr. Monia Marzouki
Dr. Sebastien Perreault (neuro-onc)
 
Social worker/patient navigator contact
Marie-Claude Charrette
 
Clinical research contact
Marie Saint-Jacques
 

 

 

Study Description

Brief Summary:

The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). NTRK gene changes lead to abnormal proteins called TRK fusion proteins, which may cause cancer cells to grow. Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Detailed Description:

The primary objectives are to determine the safety and efficacy of oral larotrectinib in pediatric patients with advanced solid or primary central nervous system (CNS) tumors.

The secondary objectives comprise e.g. the determination of the pharmacokinetic properties, the maximum tolerated dose/ recommended dose and the tumor-type specific efficacy of larotrectinib. In addition, pain status and health-related quality of life of the pediatric patients will be assessed.

Inclusion Criteria
  • Phase 1:

    • Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment.
    • Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing.
  • Phase 2:

    • Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing) (identified through molecular assays as routinely performed at CLIA or other similarly certified laboratories). Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor's Medical Monitor.
  • Patients with primary CNS tumors or cerebral metastasis
  • Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
  • Adequate hematologic function
  • Adequate hepatic and renal function
Exclusion Criteria
  • Major surgery within 14 days (2 weeks) prior to C1D1
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
  • Phase 2 only:

    • Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.
Publications

Bielack SS, Cox MC, Nathrath M, Apel K, Blattmann C, Holl T, Jenewein R, Klenk U, Klothaki P, Müller-Abt P, Ortega-Lawerenz S, Reynolds M, Scheer M, Simon-Klingenstein K, Stegmaier S, Tupper R, Vokuhl C, von Kalle T. Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion. Ann Oncol. 2019 Nov;30 Suppl 8:viii31-viii35. doi: 10.1093/annonc/mdz382. Epub 2019 Dec 24.

Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Tahara M, Pfister SM, Witt O, Ladanyi M, Rudzinski ER, Nanda S, Childs BH, Laetsch TW, Hyman DM, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020 Apr;21(4):531-540. doi: 10.1016/S1470-2045(19)30856-3. Epub 2020 Feb 24.

Bielack SS, Cox MC, Nathrath M, Apel K, Blattmann C, Holl T, Jenewein R, Klenk U, Klothaki P, Müller-Abt P, Ortega-Lawerenz S, Reynolds M, Scheer M, Simon-Klingenstein K, Stegmaier S, Tupper R, Vokuhl C, von Kalle T. Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion. Ann Oncol. 2019 Nov 1;30(Suppl_8):viii31-viii35. doi: 10.1093/annonc/mdz382.

DuBois SG, Laetsch TW, Federman N, Turpin BK, Albert CM, Nagasubramanian R, Anderson ME, Davis JL, Qamoos HE, Reynolds ME, Cruickshank S, Cox MC, Hawkins DS, Mascarenhas L, Pappo AS. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer. 2018 Nov 1;124(21):4241-4247. doi: 10.1002/cncr.31701. Epub 2018 Sep 11.

Laetsch TW, DuBois SG, Mascarenhas L, Turpin B, Federman N, Albert CM, Nagasubramanian R, Davis JL, Rudzinski E, Feraco AM, Tuch BB, Ebata KT, Reynolds M, Smith S, Cruickshank S, Cox MC, Pappo AS, Hawkins DS. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018 May;19(5):705-714. doi: 10.1016/S1470-2045(18)30119-0. Epub 2018 Mar 29. Erratum in: Lancet Oncol. 2018 May;19(5):e229.

Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018 Feb 22;378(8):731-739. doi: 10.1056/NEJMoa1714448.

LOXO-RET-18036 (LOXO 292) - A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors

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LOXO-RET-18036 (LOXO 292) - A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors

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DiagnosisSolid or brain tumour with a change in the RET geneStudy StatusOpen
PhaseI/II
AgeChild, Adult - (6 Months to 21 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationSelpercatinib is taken by mouth (capsules or oral suspension) Participants <18 years of age may be offered to try a tablet formulation of selpercatinib.
Last Posted Update2024-01-03
ClinicalTrials.gov #NCT03899792
International Sponsor
Loxo Oncology, Inc.
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Daniel Morgenstern
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

 

 

Study Description

Brief Summary:

This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.

Detailed Description:

This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, participants will be enrolled using a rolling 6 dose escalation scheme. The starting dose of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice a day (BID). Once the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is identified, participants will be enrolled to one of four phase 2 dose expansion cohorts depending on tumor histology and tumor genotype. Cycle length will be 28 days.

With a recent amendment, stable patients who have been on study for over 2 years may discuss the option of a drug treatment holiday with their clinical team. 

Inclusion Criteria
  • Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
  • Evidence of an activating RET gene alteration in the tumor and/or blood
  • Measurable or non-measurable disease
  • Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
  • Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
  • Adequate hematologic, hepatic and renal function.
  • Ability to receive study drug therapy orally or via gastric access
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion Criteria
  • Major surgery within two weeks prior to planned start of LOXO-292
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
  • Clinically significant active malabsorption syndrome
  • Pregnancy or lactation
  • Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
  • Uncontrolled symptomatic hypercalcemia or hypocalcemia
  • Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
  • Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])

DCL-17-001 - An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children and AYA with Select Solid Tumors, Lymphoma, and Malignant Brain Tumors (CLOVER-2) and Expansion in Children, AYA with Relapsed or Refractory High Grade Glioma

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DCL-17-001 - An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children and AYA with Select Solid Tumors, Lymphoma, and Malignant Brain Tumors (CLOVER-2) and Expansion in Children, AYA with Relapsed or Refractory High Grade Glioma

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DiagnosisGlioblastoma, Astrocytoma, Oligodendroglioma, Mixed Glioma, Pleomorphic Xanthoastrocytoma, Ganglioglioma, DIPG, Ependymoma Study StatusOpen
PhaseI/II
AgeChild, Adult - (10 years to 25 years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationCLR 131 administered intravenously, fractionated dose Arm 1: two planned cycles, 20 mCi/m2 on day 1 and day 15 Arm 2: three planned cycles, 10mCi/m2 on day 1 and day 15
Last Posted Update2023-11-10
ClinicalTrials.gov #NCT03478462
International Sponsor
Cellectar Biosciences, Inc.
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Daniel Morgenstern
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

 

 

Study Description

Brief Summary:

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory High Grade Glioma (HGG) for which there are no standard treatment options with curative potential.

Part A for Solid Tumors, Lymphoma, and Malignant  Brain Tumors is now closed. This study is exclusively enrolling on Part B for HGG

 

Detailed Description:

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Inclusion Criteria
  • Previously confirmed (histologically or cytologically) HGG that is clinically or radiographically suspected to be relapsed, refractory, or recurrent. Patients with DIPG are exempt from histologic verification if they have typical MRI findings of DIPG (i.e., hypo- or isointense on T1-weighted imaging, hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons, greater than 50% of pons involved) and the risk of tumor biopsy is prohibitive
  • Patient is ≥ 10 years and ≤ 25 years of age at time of consent/assent
  • Patients ≥ age 16 years must have a Karnofsky performance status of ≥ 60. Patients < age 16 years must have a Lansky performance status of ≥ 60
  • Patients must meet the following lab criteria:
    • Platelets ≥ 75,000/µL [75 x 109 /L] (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
    • Absolute neutrophil count ≥ 750/µL [0.75 x109/L]
    • Hemoglobin ≥ 8 g/dL [80 g/L] (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
    • Using the bedside Schwartz formula [Schwartz 2009], estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
    • Alanine aminotransferase < 3 × ULN
    • Bilirubin < 2 × ULN
  • At least 1 measurable intracranial lesion with longest diameter of at least 10 mm on any imaging sequence.
  • Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator’s discretion.
  • If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.
  • Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
  • Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
  • Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
  • Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible harm to the fetus.

 

Exclusion Criteria
  • Antitumor therapy or investigational therapy, within three-half-lives of the agent preceding the present study. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. Palliative focal radiation to non-target lesions should be completed at least 2 weeks prior to dosing. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial.
  • History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.)
  • Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  • Major surgery within 6 weeks of enrollment unless delay in therapy poses unacceptable risk to the patient due to clinical progression (enrollment of such patients should be discussed with Medical Monitor).
  • Known history of human immunodeficiency virus or uncontrolled, serious, active infection.
  • Pregnancy or breastfeeding
     

ACNS1422 - A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

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ACNS1422 - A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

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DiagnosisMedulloblastomaStudy StatusOpen
PhaseII
Age3 Years to 21 YearsRandomisationNO
Line of treatmentFirst line treatment
Routes of Treatment AdministrationChemotherapy: Cisplatin (Given IV), Cyclophosphamide (Given IV), Lomustine (Given PO), Vincristine Sulfate (Given IV or via minibag) Radiation: Radiation Therapy
Last Posted Update2023-11-09
ClinicalTrials.gov #NCT02724579
International Sponsor
Children's Oncology Group
Principal Investigators for Canadian Sites
Alberta Children's Hospital - Dr. Victor Lewis
BC Children's Hospital - Dr. David Dix
CancerCare Manitoba - Dr. Ashley Chopek
Janeway Child Health Centre - Dr. Lisa Goodyear
IWK Health Centre - Dr. Craig Erker
McMaster Children's Hospital at Hamilton Health Sciences - Dr. Uma Athale
Western Children's Hospital - Dr. Shayna Zelcer
Children's Hospital of Eastern Ontario - Dr. Donna Johnston
Hospital for Sick Children - Dr. Vijay Ramaswamy
Montreal Children's Hospital - Dr. Genevieve Legault
Saskatoon Cancer Centre - Dr. Kathleen Felton
Centres
Medical contact
Dr. Victor Lewis

 

Social worker/patient navigator contact
Wendy Pelletier
Clinical research contact
Debra Rich
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Dr. Magimairajan Vanan
Social worker/patient navigator contact
Rhéanne Bisson
 
Clinical research contact
Rebekah Hiebert
Megan Ridler
Kathy Hjalmarsson

 

 

Medical contact
Dr. Paul Moorehead
 
Social worker/patient navigator contact
Stephanie Eason
 
Clinical research contact
Bev Mitchell
 
Medical contact
Dr. Craig Erker
Dr. Conrad Fernandez 
Dr. Ketan Kulkarni 
 
Social worker/patient navigator contact
Rhonda Brophy
 
Clinical research contact
Tina Bocking
 
Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 
Medical contact
Dr. Alexandra Zorzi
Dr. Shayna Zelcer
 
Social worker/patient navigator contact
Cindy Milne Wren
Jessica Mackenzie Harris
 
Clinical research contact
Mariam Mikhail
Medical contact
Dr. Donna Johnston
Dr. Lesleigh Abbott
Dr. Doaa Abdel Fattah
 
Social worker/patient navigator contact
Sherley Telisma
 
Clinical research contact
Carol Duchenne
 
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact
Dr. Chris Mpofu

 

 

Social worker/patient navigator contact
Jillian Galambos
La Rae Beebe

 

Clinical research contact
Susan Kaban

 

 

 

Study Description

This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Inclusion Criteria
  • Patients must be newly diagnosed and have:

    • Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1:

      • Classical histologic type (non LC/A) WNT medulloblastoma
      • Positive nuclear beta-catenin by immunohistochemistry (IHC)
      • Positive for CTNNB1 mutation
      • Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)
  • Patient must have negative lumbar cerebrospinal fluid (CSF) cytology
    • Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status; patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated; patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
  • Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with gadolinium must be performed
  • Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (day 0)
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 100,000/uL (transfusion independent)
  • Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
    • 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
    • 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
    • 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
    • 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
    • >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
      • The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
  • Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L
  • Central nervous system function defined as:
    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
    • Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment
  • Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and neurocognitive assessments; if a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted
  • All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria
  • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
  • Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
  • Pregnancy and Breast Feeding
    • Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
    • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
  • Patients with a history of moderate to profound intellectual disability (i.e., intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study

Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team.