NCT02901145

Nivolumab in Relapsed Pediatric Solid Tumors

A Phase I/II Clinical Trial of Nivolumab in Progressive/Relapsed Pediatric Solid Tumors

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Hadassah Medical Organization · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

patients with progressive/relapsed solid tumors who failed first line therapy , will be treated biweekly with the anti PD1- Nivolumab. at least one month after treatment initiation low dose cyclophosphamide will be started . patients on trial will submit tissue and blood tests for whole exome an immune genomic signature. patients will also undergo repeated immunophenotype as part of follow up.

Detailed description

Programmed cell death 1 (PD-1) is an inhibitory receptor that prevents immune activation. PD-1 blockade can mediate reactivation of immune mediated tumor killing leading to tumor regression . Another mechanism of tumor associated immune inactivation is elevation of rates of T regulatory cells. This process may be prevented by treatment with low dose cyclophosphamide. Objective: This study will evaluate safety and tolerability of the anti PD1 antibody Nivolumab combined with other immunomodulating treatments, in pediatric patients with relapsed/progressive solid tumors Method: Patients will be treated with IV Nivolumab 3mg/kg over 60 minutes on day 1 and 15 of each cycle of 28 days. 1. Dose finding phase: 1. Six patients will be accrued for the first cohort and treated for 1 month 2. If an adverse event \>grade 2 will occur in\>2 patients, study medication dose will be reduced by 25% and another cohort of 6 patients will be accrued on the reduced dose. 3. Dose finding cohorts will be accrued until determination of a dose with allowed DLT 2. Expansion phase 1. Following dose determination patients will be accrued, to the final number of 30 patients 2. Cyclophosphamide at the dose of 50 mg/dayx7days every 14 days (one week on one week off ) will be started . immunophenotype will be done every 28 days and dose of cyclophosphamide will be elevated by 25mg /day every month until highest ratio of CD8/CD25FOXP3 cells will be reached for every child 3. All patients will be treated for 1 year or until imaging proven disease progression. 3. Required follow up 1. All patients will undergo tumor bed imaging (CT/MRI-based on tumor location) with metastatic evaluation (according to standar follow up) every 4 months 2. Tumor response will be measured based on RECIST criteria 3. Toxicity assessment will be done according to the CTCAE v. 4.03 c. Collateral studies: 1. Immunohistochemical analysis for PD1 and PDL1 will be done on pretreatment paraffin embedded tissue to estimate it's ability to predict response. 2. Immune profile of peripheral blood lymphocytes including CD3+, CD4+, CD8+ FOX P3+ cells and it's correlation to objective response to therapy. 3. Exome sequencing of the tumor and peripheral blood will be done for every patient. Exome will be evaluated for driver mutations and immunologic genomic signature.

Conditions

• Antibodies, Neoplasm

Interventions

Type	Name	Description
DRUG	Nivolumab,low dose cyclophosphamide	treatment with IV Nivolumab 3mg/kg every 2 weeks . after a month-addition of low dose cyclophosphamide at a starting dose of 50 mg/kg/day x7 days every 14 days with dose adaptation based on level of Tregulatory cells on follow up immunophenotype.

Timeline

• Start date: 2016-11-01
• Primary completion: 2019-11-01
• Completion: 2020-03-01
• First posted: 2016-09-15
• Last updated: 2016-09-15