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| Diagnosis | Refractory or Recurrent Hypermutated Malignancies, Biallelic Mismatch Repair Deficiency (bMMRD) Positive Patients, Other solid tumours, CMMRD | Study Status | Closed |
| Phase | I/II |
| Age | Child, Adult - (12 Months to 18 Years) | Randomisation | N/A |
| Line of treatment | Disease relapse or progression |
| Routes of Treatment Administration | IV |
| Last Posted Update | 2024-03-18 |
| ClinicalTrials.gov # | NCT02992964 |
International Sponsor
The Hospital for Sick ChildrenPrincipal Investigators for Canadian Sites
The Hospital for Sick Children – Dr. Daniel Morgenstern
BC Children's Hospital - Dr. Rebecca Deyell
Centres
Medical contact
Rebecca Deyell
Social worker/patient navigator contact
Ilana Katz
Clinical research contact
Hem/Onc/BMT Clinical Trials Unit
Study Description
Some cancer, called hypermutant cancer, have been shown to have multiple genetic changes or abnormalities that block DNA repair and favor tumour development. Nivolumab 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, nivolumab 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.
In this phase I/II study, patients will not be randomized and all enrolled on the clinical trial will receive nivolumab. The study will evaluate the dose, safety, tolerability, effect on the cancer and other important characteristics of nivolumab. This study includes pediatric patients with recurrent or refractory hypermutant cancer aged 12 months to 18 years, including those with bMMRD syndrome. for which no standard therapy is available or for which the subject is not eligible for the existing therapy.
Inclusion Criteria
• Patients must be greater than 2 months and less than 25 years of age at time of enrollment. Please note, some hospitals may not be able to treat patients above certain ages (e.g., 18 years old).
• Recurrent or relapse paediatric cancer suspected to be hypermutant, including those exhibiting evidence of genetic or molecular alterations such as: high microsatellite instability (MSI-H) in current or previous tumour, mutation causing loss of mismatch repair gene (MLH1, MSH2, MSH6, PMS2, EPCAM or MSH3) expression, hypermutation by local sequencing in current or previous tumour, a history of CMMRD, Lynch syndrome, xeroderma pigmentosum (XP), or other established disorder affiliated with an elevated hypermutation rate, a functional mutation of polymerase genes (POLE or POLD1) in current or previous tumour, a functionally impaired RRD pathway by other means; etc.
• Patients must have histologic or cytologic confirmation of malignancy at the time of initial diagnosis or relapse (as specified above). Patients with multiple concurrent and/or sequential neoplasms are eligible, including CNS and haematological malignancies.
• Patients must be able to provide tumour sample (archival or a new biopsy). If a tumour sample (including archival) is not available, a new tumour sample may be needed. Any such biopsy will not be considered a trial-related procedure.
Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team.
