Canadian clinical trial registry

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Study Description

This study is trying to determine the benefit of adding bevacizumab (an intravenous drug) to chemotherapy treatment with vinblastine, in children and adolescents with low grade gliomas.

Participants in this trial will be randomised (randomly assigned) into one of two treatment arms.

• Arm A will include 68 weeks (16 months) of single agent Vinblastine given once weekly intravenously.
• Arm B will include 68 weeks (16 months) of Vinblastine given weekly intravenously with the addition of 12 doses of bevacizumab given every two weeks intravenously for the initial 24 weeks (6 months).

Inclusion Criteria

• Children and adolescents aged 6 months to < 18 years
• Low grade glioma 
• The tumour must have grown back after surgery with clear imaging or clinical signs, or
• The tumour was partially removed with surgery and there is a necessity to begin treatment because of a risk of neurological impairment with progression.
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

The purpose of this study is 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 larotrectinib.

Inclusion Criteria

• Children from birth through 21 years of age
• Patient 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
• Patient must have a malignancy with a documented NTRK gene fusion.
• Patient with a 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 or a documented NTRK fusion by next generation sequencing.

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

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.

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Study Description

Philadelphia-like leukemia has specific genetic changes. This study is to assess the dose and effectiveness of an oral medication called ruxolitinib that targets Philadelphia-like leukemia cells. It blocks a protein called JAK. The medication is given in addition to standard therapy for the leukemia. 

Based on the leukemia genetics and initial response to treatment, patients are divided into 4 groups. 

Inclusion Criteria

• Patients between 1 and 21 years of age
• New diagnosis of Philadelphia-like, high-risk B-cell acute lymphoblastic leukemia
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

This phase III trial compares the effect of two chemotherapy drug pathways (vinorelbine with vincristine, dactinomycin, and cyclophosphamide (VAC) followed by vinorelbine and cyclophosphamide versus VAC followed by vinorelbine and cyclophosphamide) for the treatment of high risk rhabdomyosarcoma.

Chemotherapy drugs, such as vinorelbine, vincristine, dactinomycin, and cyclophosphamide, 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 vinorelbine and VAC may kill more tumor cells and adding maintenance therapy after VAC therapy may help get rid of the cancer and/or lower the chance that the cancer comes back.

Inclusion Criteria

• Patients must be =< 50 years of age 
• Study is open to all genders
• Patients with newly diagnosed rhabdomyosarcoma (RMS) of any subtype, meeting "high risk" criteria
• Various bloodwork (bilirubin, creatinine, etc) must be within an acceptable range
• Patients must not be pregnant during the duration of the trial
• Additional inclusion and exclusion criteria may apply and will be reviewed by the study team

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Study Description

The purpose of this study is to evaluate the safety and efficacy of combining Focused Ultrasound (Exablate Model 4000 Type 2.0/2.1) with Doxorubicin therapy for the treatment of DIPG in pediatric patients.

Inclusion Criteria

• Age between 5 and 18 years, inclusive
• Patient diagnosed with DIPG
• Must be between 4-12 weeks from completion of radiation therapy
• Able to attend all study visits
• Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
• If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable

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

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Study Description

Some neuroblastoma have a specific genetic change or mutation called an ALK aberration.  ALK, or anaplastic lymphoma kinase, has been found in several adult and pediatric cancers.  ALK aberrations are present in about 14% of newly diagnosed patients with high-risk neuroblastoma, and can be found more frequently at the time of relapse.  Lorlatinib is a drug called an ALK inhibitor. It is expected to slow or stop the growth of cancer cells which have the ALK aberration. The aim of this phase I/II study is to evaluate the dose, safety, and tolerability of lorlatinib, including the effect it has on the cancer.  Lorlatinib will be given alone or in combination with chemotherapy in children with refractory, relapsed or progressive neuroblastoma with ALK alterations.

Inclusion Criteria

• Patients must have a diagnosis of neuroblastoma either by histologic verification (looking at a sample of the tumour under a microscope) of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines (HVA/VMA).
• Patients are required to have an activating ALK aberration in their tumor, which is identified through genetic testing.
• Patients must have high risk neuroblastoma. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
• Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease

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 tests the safety, best dose, and whether elimusertib works in treating patients with solid tumors that have come back (relapsed) or does not respond to treatment (refractory). Elimusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

• Age Restrictions: 
  • Part A:
    • Patients between >= 12 months and < 18 years of age
  • Part B:
    • Patients between >= 12 months and =< 30 years of age for the phase 2 expansion cohorts for both EWS and PAX3-FOXO1 ARMS.
    • Patients between >= 12 months and =< 21 years of age for the phase 2 DDR expansion cohort
• Patients must be able to swallow tablets of the study drug (elimusertib)
• Patients must have a solid tumor diagnosis that has come back (relapsed) or has not respond to treatment (refractory)
  • NOTE: further restrictions may apply for each cohort and will be discussed with you by the clinical team
• Patients must have measurable disease
• Patients must be up and about at least half of their waking hours
• Bloodwork requirements must be met prior to treatment
• Patients must meet the minimum duration from any prior anti-cancer therapy before enrolling. These timelines will be discussed with you by the clinical team.  
• Patients or their substitute decision maker must sign a consent form and agree to the required study assessments

Additional inclusion and exclusion crieria may apply 

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Study Description

This is a study of pembrolizumab (antibody against a marker called PD1) in children and adolescents who have any of the following types of cancer:

• advanced melanoma (now only open for patients age 12-18)
• advanced, relapsed or refractory cancer (except brain tumours and leukemia) that have this PD1 marker (now closed) 
• relapsed or refractory classical Hodgkin lymphoma 
• advanced relapsed or refractory cancer (except brain tumours and leukemia) that is known to be "microsatellite-instability-high (MSI-H)"
• advanced relapsed or refractory cancer (except brain tumours and leukemia) that is known to be "tumor-mutational burden-high" (TMB-H)"

Pembrolizumab is a human monoclonal antibody that binds and blocks PD-1 on tumors cells.  The PD-1 pathway is an immune system checkpoint that may be used by cancer tumour cells to help them trick the immune system (escape surveillance) and avoid being destroyed. By blocking the PD-1 pathway, pembrolizumab reactivates cells from the patient immune system to help it identify and destroy the cancer cells. It is expected to slow or stop the growth of cancer cells.

This study has two parts. Part 1 will find the recommended dose for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy of pembrolizumab therapy.

Inclusion Criteria

• Age between 6 months and <18 years  (or between 3 years and <18 years of age for participants with Hodgkin's lymphoma) 
• Locally-advanced, or metastatic cancer (except brain tumours and leukemia) that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate. The cancer type has to meet one of the following types described in the "study description" section.
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

Publications

Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo A, Laetsch TW, Petrilli AS, Ebinger M, Toporski J, Glade-Bender J, Nicholls W, Fox E, DuBois SG, Macy ME, Cohn SL, Pathiraja K, Diede SJ, Ebbinghaus S, Pinto N. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Jan;21(1):121-133. doi: 10.1016/S1470-2045(19)30671-0. Epub 2019 Dec 4.