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

Childhood Solid Tumor Clinical Trial

Official title: Metro-PD1: a Phase I/II Trial Evaluating Anti-PD1 (Nivolumab) in Combination With Metronomic Chemotherapy in Children and Teenagers With Refractory / Relapsing Solid Tumors

Status Active, not recruiting

Clinical Trial Summary

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

Clinical Trial Description

1. First stage (closed):

• Arm A: Nivolumab + Cyclophosphamide-Vinblastine

• Arm B: Nivolumab + Capecitabin

• Arm C: Nivolumab + Cyclophosphamide-Vinblastine + Capecitabin

Arm A and Arm B have been allocated sequentially (A/B/A/B/A/B). Arm C has been opened, since arm A and Arm B were deemed safe.

In each arm, the second patient was not recruited before the first patient has been observed for a 28-day duration.

2. Second stage (opened):

Following the analysis of safety data from first stage, and according to IDMC's recommendations on December 2020, the metronomic chemotherapy selected for second stage was arm C: cyclophosphamide, capecitabine, vinblastine

Randomization will be balanced 1:1, controlling for:

• histological type: embryonal brain tumor, ependymoma, low-grade glioma, rhabdomyosarcoma, neuroblastoma, Ewing sarcoma, and other solid tumors after approval from coordinators,

• and treating center, using a dynamic allocation of treatment (minimization program) with a random factor set at 0.8.

3. Trans-MetroPD1 is divided into 3 axes:

• to evaluate the health-related quality of life

• to measure the kinectis of progastrin/hPG80, a biomarker over-expressed in a wide range of cancers

• to determine the distribution of immune cells within blood tissue ;

Related Conditions & MeSH terms

• Childhood Solid Tumor
• Neoplasms

• NCT number: NCT03585465
• Study type: Interventional
• Source: Centre Oscar Lambret
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 26, 2019
• Completion date: January 2028