Canadian clinical trial registry

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Study Description

Many pediatric brain and solid tumors have genetic changes that do not involve changes to the underlying DNA sequence called epigenetic alterations.These dysfunctions can favor tumour developpment. 5'Azacitidine is a drug that has similarities with one of the components of DNA and RNA.

It can kill abnormal cells through incorporation into DNA and RNA. It is expected to slow or stop the growth of cancer cells.

The aim of this phase I/II study is to evaluate the dose, safety, tolerability, antitumor activity and other characteristics of 5'azacytidine in combination with carboplatin.

Inclusion Criteria

• Greater than the age of 1 year and under age 18 at the time of study enrolment
• Recurrent or refractory solid tumor (Phase I), or recurrent or refractory ependymoma (Phase Ib)
• Tissue from diagnosis or resection prior to registration must be available (either flash frozen tissue or an FFPE (formalin fixed paraffin embedded) block)
• Previous therapy with carboplatin will be permitted
• Failed first line treatment (surgery, radiation therapy or chemotherapy) and should not be eligible for treatment with curative potential.

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

Publications

Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature. 2014 Feb 27;506(7489):445-50. doi: 10.1038/nature13108. Epub 2014 Feb 19.

Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen ML, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DP, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognár L, Klekner A, Hortobágyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tuñon T, Schüller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher PG, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, Taylor MD. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol. 2016 Jul 20;34(21):2468-77. doi: 10.1200/JCO.2015.65.7825. Epub 2016 Jun 6.

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Study Description

Some diseases such as cancer with BRAF mutations, low grade gliomas and plexiform neurofibroma in patients with neurofibromatosis type 1 [NF-1], or Langerhans cell histocytosis [LCH]) have been shown to have molecular dysfunction called MAPK pathway dysregulation which favors tumour development. The MAPK pathway is involved in cell growth, differentiation, inflammation and apoptosis.Trametinib is an inhibitor of components of the MAPK pathway called MEK1 and MEK2. Drabafenib is a small molecule that inhibits the MAPK pathway in BRAF mutated cells by blocking the BRAF serine-threonine kinase. Both are expected to slow or stop the growth of cancer cells.

The aim of this phase I/II study is to evaluate the dose, safety, tolerability, antitumor activity and other pharmacologic characteristics of Trametinib alone or with Dabrafenib in children with refractory or relapsed solid cancer or disease with BRAF mutations for which no standard therapy is available or for which the subject is not eligible for the existing therapy.

The study is currently open for LCH and neuroblastoma only.

Inclusion Criteria

• Male or female between one month and <18 years of age (inclusive) at the time of signing consent
• Must have a disease that is relapsed/refractory to all potentially curative standard treatment regimens or must have a current disease for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
• The subject's disease (i.e. cancer, neurofibromatosis type 1 [NF-1] with plexiform neurofibroma [PN], or Langerhans cell histocytosis [LCH]) must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities
• Able to swallow and retain enterally administered medication

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

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Study Description

Some rare cancer such as rhabdoid tumors or epithelioid sarcoma have been shown to have a molecular dysfunction allowing a protein called EZH2 to favour tumour developpment. Tazemetostat is an EZH2 inhibitor and is expected to slow or stop the growth of cancer cells. The aim of this Phase I study is to evaluate the dose, safety, tolerability, antitumor activity and other pharmacologic characteristics of Tazemetostat in children with refractory or relapsed solid cancer  for which no standard therapy is available or for which the subject is not eligible for the existing therapy. 

Inclusion Criteria

• Age ≥6 months to <18 years
• Patient has one of the specific disease targeted in this study, histologically confirmed by a CLIA/CAP certified laboratory
• Relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion
• Patient is able to swallow and retain orally administered medication

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

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Study Description

This phase I/II trial is trying to determine how much carfilzomib (an anti-cancer drug) should be used, alone and in combination with induction chemotherapy, to treat children with acute lymphoblastic leukemia that has come back (relapsed) or is refractory to treatment. Carfilzomib is an anti-cancer medication called proteasome inhibitor and is given intravenously.

Inclusion Criteria

• Age 1 year to 21 years
• Acute lymphoblastic leukaemia that has come back (relapsed) or is refractory to treatment
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

This study is specifically for patients diagnosed with relapsed or persistent neuroblastoma.

Metaiodobenzylguanidine (MIBG) is a compound that can be combined with radioactive iodine (I-131) to deliver targeted radiation therapy. Oncologists use to deliver targeted radiation to neuroblastoma. I-131 MIBG is administered to a child through an intravenous line and is absorbed by tumor cells, which are killed by radiation emitted by the radioactive I-131. 

The three treatment arms are the following:

• 131 I-MIBG therapy alone
• 131 I-MIBG therapy with Irinotecan and Vincristine: The two chemotherapy medications irinotecan and vincristine, which are known to be active agents for neuroblastoma, are given at the same time as the ¹³¹I-MIBG, and may make the ¹³¹I-MIBG more effective at treating neuroblastoma.
• 131 I-MIBG with Vorinostat: Vorinostat is a drug that is FDA-approved to treat a certain type of cancer mainly seen in adults. Vorinostat affects the way the DNA that carries our genes is folded in cells. In the laboratory, vorinostat causes neuroblastoma cells to stop growing. This effect is even greater when vorinostat is combined with radiation. Giving vorinostat together with the ¹³¹I-MIBG may make the ¹³¹I-MIBG more effective at treating neuroblastoma.

Why is this study being done?

• To find out which of the three ¹³¹I-MIBG treatment arms have a better tumor response rate
• To compare the side effects seen with ¹³¹I-MIBG alone, compared with ¹³¹I-MIBG in combination with Vincristine and Irinotecan or  ¹³¹I-MIBG with Vorinostat.
• To describe the number of patients found to have tumor cells in the blood and bone marrow using a new sensitive test following each of the three ¹³¹I-MIBG treatment arms.
• To compare the exposure of whole body radiation from ¹³¹I-MIBG received on the three treatment arms.
• To learn about a new computerized way of reading MIBG scans.

Inclusion Criteria

(From NANT website - https://www.nant.org/n2011-01/)

• Patients must be at least 24 months and no older than 30 years of age
• Patients must have relapsed neuroblastoma, refractory neuroblastoma or persistent neuroblastoma 
• Patients must have  at least one site of tumor with MIBG uptake based on an MIBG scan done within 4 weeks prior to entry on study
• Patients must have an adequate number of  peripheral blood stem cells available.
• Patients must have adequate organ function.
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

Nivolumab is a type of therapy called immunotherapy that works by attempting to help the body's immune system attack the cancer. This study is to assess the effectiveness of  nivolumab on relapsed or refractory solid tumors in children. The maximum tolerated dose and recommended dose for children will be explored. The study also looks at the side effects associated with this medication. Based on the tumor type, patients are categorized into Parts A through E and receIve nivolumab in recurring cycles. 

Inclusion Criteria

• There are multiple parts to this study. Some parts include children between 1 and 18 years old, while others include patients between 1 and 30 years old
• Different types of recurrent or refractory solid tumors are included in this study including neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, peripheral primitive neuroectodermal tumor (PNET), Hodgkin lymphoma, non-Hodgkin lymphoma and melanoma 
• Patients with brain tumors or brain metastases from their cancer are not included in this study 
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

Publications

Davis KL, Fox E, Merchant MS, Reid JM, Kudgus RA, Liu X, Minard CG, Voss S, Berg SL, Weigel BJ, Mackall CL. Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Apr;21(4):541-550. doi: 10.1016/S1470-2045(20)30023-1. Epub 2020 Mar 17.

Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14. Review.