NCT03585465

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

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: Centre Oscar Lambret · Academic / Other
• Sex: All
• Age: 0 Years – 18 Years
• Healthy volunteers: Not accepted

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

Detailed 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

Conditions

• Childhood Solid Tumor

Interventions

Type	Name	Description
DRUG	Vinblastine	* 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
DRUG	Cyclophosphamide	* 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
DRUG	Capecitabine	* 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
DRUG	Nivolumab	* 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

Timeline

• Start date: 2019-03-26
• Primary completion: 2025-12-31
• Completion: 2027-01-01
• First posted: 2018-07-13
• Last updated: 2026-03-18

Locations

11 sites across 2 countries: Belgium, France