Canadian clinical trial registry

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Study Description

The purpose of this research study is to investigate an experimental drug, MK-3475 (also called pembrolizumab), in young patients. The drug MK-3475 has been previously studied in adults, in a variety of tumors, but is not yet FDA approved. The first phase is a safety study to assess side effects and best dose of pembrolizumab, the second phase is the efficacy portion to see how well it works in treating childhood brain tumors that have come back (recurrent), progressed, or not responded (refractory) to previous treatment. 

(transcribed from PBTC-045 Summary for Patients and Families)

Inclusion Criteria

• Patient must have one of the following diagnoses that have come back, progressed or not responded to treatment, to be eligible: 
  • Stratum A : DIPG - currently closed to enrollment
  • Stratum B : Non-brainstem high-grade glioma (NB-HGG)
  • Stratum C : Hypermutated brain tumor
  • Stratum D : Ependymoma
  • Stratum E : Medulloblastoma 
• Patient must have been treated with prior radiation therapy and/or chemotherapy (exclusions apply)
• Both males and females of all races and ethnic groups are eligible for this study
• Patient must be able to be up and about more than 50% of their waking hours
• Age Requirements:
  • Stratum A  -  1 year to 18 years old during safety portion, <22 years during efficacy, currently closed to enrollment
  • Stratum B  - 1 year to 18 years old during safety portion, <22 years during efficacy
  • Stratum C  - Younger than 30 years old
  • Stratum D  - 1 year to 18 years old during safety portion, <22 years during efficacy
  • Stratum E  - 1 year to 18 years old during safety portion, <22 years during efficacy
• Patients must have satisfactory blood work prior to enrolling
• Patient must not have any shortness of breath
• Human immunodeficiency virus (HIV)-infected patients with undetectable viral load within 6 months are eligible for this trial
• Patients of child bearing potential must NOT be pregnant, and must agree to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity while on study and 6 months after
• Patient and/or guardian must sign a written consent document

Additional inclusion and exclusion criteria may apply.

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Study Description

(As seen on the Australian & New Zealand Childrens Haematology/Oncology Group website - https://anzchog.org/clinic-trails/connect-1903-a-pilot-and-surgical-study-of-larotrectinib-for-treatment-of-children-with-newly-diagnosed-high-grade-glioma-with-ntrk-fusion/ )

Recent research shows that a new oral tablet drug, larotrectinib, has produced promising results by shrinking some solid tumours that have an abnormal or mutated NTRK gene in adults and children.

High grade gliomas (HGG) are fast growing, aggressive brain cancers and if they recur after initial treatment, there are no effective treatment options. This study will investigate if larotrectinib alone as well as Larotrectinib  in combination with chemotherapy or radiotherapy can  be of benefit in children with high grade gliomas with the mutated NTRK gene. This international trial will study how well the drug is tolerated and its effectiveness to shrink these tumours when used alone or when given with standard chemotherapy or after radiation.

Inclusion Criteria

(As seen on the Australian & New Zealand Childrens Haematology/Oncology Group website - https://anzchog.org/clinic-trails/connect-1903-a-pilot-and-surgical-study-of-larotrectinib-for-treatment-of-children-with-newly-diagnosed-high-grade-glioma-with-ntrk-fusion/ )

• Patient must be 21 years old or younger and newly diagnosed with high grade glioma (HGG)
• The tumour must have a genetic anomaly called an NTRK fusion for the patient to qualify
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

This clinical trial studies the side effects and how well a chemoplaque with topotecan (a medication attached to the outside of the eye) works in treating patients with retinoblastoma. This plaque has to be installed and removed under general anesthesia by the ophthalmology team. It delivers the chemotherapy inside the eye.

Inclusion Criteria

• Age up to 18 years
• Retinoblastoma in at least one eye
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

MEKTOVI (binimetinib) is a medicine taken by mouth that helps block certain signals in the body that make some tumors grow. In this Phase II study, the drug will be used to treat children diagnosed with Adamantinomatous Craniopharyngioma (ACP), a type of brain tumor. This tumor can be very challenging to treat, and current options like surgery and radiation can affect the patient's quality of life, especially when the tumor comes back.

Recent research shows that ACP might respond to medicines like binimetinib that block specific pathways in the body.

Up to 38 children will take binimetinib in pill form, twice a day for 4 weeks (1 cycle), and treatment could continue for up to two years. The trial will include children aged 1 to 25, some of whom have already had radiation therapy.

The goal is to see if this medicine can help control the tumor and improve their quality of life.

Inclusion Criteria

• Patients must be between 1 and 25 years old.
• Must have a confirmed Adamantinomatous Craniopharyngioma (ACP), either from a solid tumor or cyst fluid.
• Must have a measurable tumor that can be seen on scans:
  • Stratum 1: Patients whose tumor came back or got worse at least 6 months after finishing radiation therapy.
  • Stratum 2: Patients who have had surgery but have not had radiation (they may have had other treatments before).
• Patients must be able to do at least half of their usual activities, even if they use a wheelchair.
• Must have recovered from any side effects of previous treatments.
• Previous Treatments:
  • At least 7 days since the last dose of any biologic treatment (anti-tumor therapy).
  • At least 42 days since any immunotherapy (e.g. cancer vaccines).
  • At least 21 days since a monoclonal antibody treatment.
  • At least 6 months since focused radiation and no history of radiation to the whole brain/spine.
  • Corticosteroids: If on dexamethasone, the dose must be stable or reducing for at least 1 week.
  • Chemotherapy: At least 21 days since the last round of chemotherapy.
  • Surgery: At least 6 weeks since any surgery.
• Blood counts and organ function requirements must meet certain safety levels before treatment.
• Patient and/or their parent/guardian must agree to join the study by signing a consent form.

Additional inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

Publications

• Foreman NK, Faestel PM, Pearson J, Disabato J, Poole M, Wilkening G, Arenson EB, Greffe B, Thorne R. Health status in 52 long-term survivors of pediatric brain tumors. J Neurooncol. 1999 Jan;41(1):47-53. doi: 10.1023/a:1006145724500.
• Goldman S, Pollack IF, Jakacki RI, Billups CA, Poussaint TY, Adesina AM, Panigrahy A, Parsons DW, Broniscer A, Robinson GW, Robison NJ, Partap S, Kilburn LB, Onar-Thomas A, Dunkel IJ, Fouladi M. Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2020 Nov 26;22(11):1696-1704. doi: 10.1093/neuonc/noaa119.
• Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Holsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018 May;135(5):757-777. doi: 10.1007/s00401-018-1830-2. Epub 2018 Mar 14.
• Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017 Jun 15;144(12):2141-2152. doi: 10.1242/dev.150490. Epub 2017 May 15.
• Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2.
• Watanabe K, Otsu S, Hirashima Y, Morinaga R, Nishikawa K, Hisamatsu Y, Shimokata T, Inada-Inoue M, Shibata T, Takeuchi H, Watanabe T, Tokushige K, Maacke H, Shiaro K, Ando Y. A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1157-64. doi: 10.1007/s00280-016-3019-5. Epub 2016 Apr 12.
• Patel K, Allen J, Zagzag D, Wisoff J, Radmanesh A, Gindin T, Nicolaides T. Radiologic response to MEK inhibition in a patient with a WNT-activated craniopharyngioma. Pediatr Blood Cancer. 2021 Mar;68(3):e28753. doi: 10.1002/pbc.28753. Epub 2020 Oct 19. No abstract available.

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Study Description

This trial is looking at whether adding a medicine called melphalan (which is injected into the eye) to regular chemotherapy can help treat children with retinoblastoma, a type of eye cancer. Retinoblastoma can sometimes be harder to treat when there are tiny bits of the tumor floating in the jelly-like part of the eye - called vitreous seeds. Melphalan, along with other chemotherapy drugs, works by stopping cancer cells from growing and dividing. The goal of this study is to see if adding melphalan early in treatment can better target those floating tumor bits and improve treatment for retinoblastoma.

Inclusion Criteria

• Must be under 18 years old
• The child must have a new diagnosis of retinoblastoma (a type of eye cancer) that is still in the eye 
• Participant must meet one of the following conditions: 
  • Retinoblastoma in one eye (Group D) with tumor pieces floating in the eye fluid.
  • Retinoblastoma in both eyes, with one eye in Group D (with tumor pieces in the fluid) and the other eye less severe (Group A-C).
  • Retinoblastoma in both eyes, with at least one eye in Group D (with tumor pieces in the fluid).
  • Retinoblastoma in both eyes, with one eye in Group D (with tumor pieces in the fluid) and the other eye in Group E (most severe), where the Group E eye was removed before any treatment.
  • Retinoblastoma in both eyes, with one eye in Group D (with tumor pieces in the fluid) and one Group E eye that hasn't been removed yet (depending on the doctor's decision).
• The child must be in good enough health to handle treatment, based on performance scores for their age.
• Blood counts and kidney function must meet certain safety levels before treatment.

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

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Study Description

This is a phase 1/2 study that studies the drug avapritinib in patients 2-17 years old with solid tumors that have come back (relapsed) or have not responded to previous treatment (refractory). The tumor must have a certain genetic mutation (in KIT, PDGFRA or H3K27M (glioma only)) to qualify you for the study. The study consists of 2 parts; in part 1, more information will be gathered about the drug's safety and how it moves through the body (pharmacokinetics or PK) and in part 2, the effectiveness, safety and PK will continued to be monitored at the recommended dose. 

Inclusion Criteria

• Patients must be between 2-17 years old
• Patients must have a diagnosed solid or central nervous system (CNS) tumor that has progressed despite prior standard therapy or no alternative treatment is available 
• Patients must be able to be up and about at least half of their waking hours (if applicable)
• Blood work must come back within acceptable ranges within 14 days of the first study dose
• Patients must not be pregnant on the trial, participants of child bearing potential must agree to use approved contraception methods
• Patients and/or their families/caregivers must sign a consent form outlining all assessments and requirements

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Study Description

This study evaluates the safety of a type of treatment called HER2 CAR T cells (short for HER2 chimeric antigen receptor T cells). In addition to looking for side effects, we will study how well this treatment works against a brain tumor called ependymoma that has come back after treatment (recurrent) or has not responded well to treatment (progressive) in children. The HER2 CAR T cells used in this trial are made from the patient's own blood.

A new gene, called the HER2 CAR, will be inserted into patient's cells to allow them to recognize a protein on the tumor called HER2. These HER2-specific CAR T cells may be able to target and kill ependymoma tumors. This research is also studying how doable it is to provide this type of CAR T cell treatment to children being treated at different hospitals.

Inclusion Criteria

• Participants must have a diagnosis of ependymoma that is has come back or progressed.
• Patient must be ≥ 1 but ≤ 22 years of age at the time of enrollment for treatment.
• Participants must be up and about for 60% of their waking hours
• Patients must have received last dose of previous chemotherapy at least 21 days before enrollment.
• Patient must meet all organ function, bone marrow function and laboratory criteria
• The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines. Age- and developmentally appropriate assent should be obtained as required by institutional guidelines.

Additional inclusion and exclusion criteria applies and will be discussed with you by the study team.

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Study Description

This is a phase I/II study that studies the drug SNDX-5613 in patients with acute leukemia. In phase 1, the dose will be increased to find the maximum tolerated dose of SNDX-5613 and the recommended dose for the next phase will be determined. In phase 2, patients will be given the recommended phase 2 dose determined in phase 1, and the safety and efficacy in patients with various tumour mutation will be studied. 

Inclusion Criteria

• Patients must have active acute leukemia with certain genetic characteristics
• Patients must be over 30 days old 
• Patients must be up and about more than 50% of waking hours (if applicable)
• Adequate time must have passed from all previous treatments (i.e at least 60 days must have passed from last radiation treatment/stem cell infusion (if applicable))
• Adeqaute organ function
• Blood work must come back within acceptable ranges
• Patients of child bearing potential must be willing to use a highly effective method of contraception from the time of enrollment to 120 days after the last study drug dose
• Patients and/or their families/caregivers must sign a consent form outlining all assessments and requirements