Nivolumab in Combination With Metronomic Chemotherapy in Paediatrics Refractory / Relapsing Solid Tumors

Conditions

• Childhood Solid Tumor

Eligibility Criteria

Sex

ALL

Age

0 Years - 18 Years

Healthy Volunteers

Not accepted

Interventions

• Vinblastine — DRUG
  * Experimentals Arm A or C (First stage): 2 mg/m2/day IV, weekly per cycle, 28 days cycle * Experimental Arms Metronomic or Metronomic+Nivolumab (second stage): see C
• Cyclophosphamide — DRUG
  * Arm A (First stage): 30 mg/m2/day PO, D1-4// D8-11// D15-18// D22-25 per cycle, 28 days cycle * Arm C (First stage): 30 mg/m2/day PO, D1-D4// D15-D18 per cycle, 28 days cycle * Metronomic or Metronomic+Nivolumab Arm (second stage): see C
• Capecitabine — DRUG
  * Arm B (First stage): 400 to 600 mg/m2/day PO, all days per cycle, 28 days cycle * Arm C (First stage): 400 to 600 mg/m2/day PO, D8-D11// D22-D25 per cycle, 28 days cycle * Metronomic or Metronomic+Nivolumab Arm (second stage): see C
• Nivolumab — DRUG
  * Arm A, B or C (First stage): 3 mg/kg IV, D1 \& D15 per cycle, 28 days cycle * Metronomic+Nivolumab Arm (second stage): 3 mg/kg IV, D1 \& D15 per cycle, 28 days cycle

Study Details

The study is a two-stage trial: 1. First stage (closed - 16 patients recruited in France): Phase I feasibility trial to evaluate the safety of the combination of Nivolumab + metronomic chemotherapy considering three possible metronomic chemotherapy regimens 2. Second stage (opened - 86 patients expected in France and Belgium): Phase II randomized controlled balanced 1:1 open-label trial comparing the efficacy of the metronomic chemotherapy regimen selected at the end of the previous stage (arm C: cyclophosphamide, capecitabine, vinblastine), with or without nivolumab. 3. "Trans-MetroPD1" ancillary sub-study is partially implemented since April 2022, and proposed to patients participating to second stage

Key Dates

Start date

Mar 26, 2019

Status verified

May 2026

Primary completion

May 31, 2025

Completion

Dec 27, 2025

Study Design

Enrollment

63 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: A: Cyclophosphamide Vinblastine Nivolumab
  This arm was applicable to first stage, and is closed
• Experimental: B: Capecitabine Nivolumab
  This arm was applicable to first stage, and is closed
• Experimental: C: Cyclophosphamide Vinblastine Capecitabine
  This arm was applicable to first stage, and is closed
• Experimental: "Metronomic CT "
  metronomic chemotherapy selected at the end of first stage (C: Cyclophosphamide Vinblastine Capecitabine) This arm is applicable to second stage, and 43 patients are expected
• Experimental: "Metronomic CT + Nivolumab"
  metronomic chemotherapy selected at the end of first stage (C: Cyclophosphamide Vinblastine Capecitabine) + Nivolumab This arm is applicable to second stage, and 43 patients are expected

Primary Outcome Measure

Dose Limiting Toxicities according to the NCI-CTCAE V5 [ Time Frame: Over the first chemotherapy cycle (28 days) ]