Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients With Refractory Solid Tumors

NCT01282697 | Completed Phase 1 DMC

• 1 other identifier: 4791
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 9

Brief Summary

Therapeutic solutions to treat solid tumors that are resistant to conventional treatments are now limited. Laboratory data in animals (on pediatric tumors such as brain tumors, sarcomas and neuroblastomas) have shown that the combination of irinotecan (HIF1alpha inhibitor) and rapamycin (mTOR inhibitor) allowed to block development of blood vessels in the tumor and could, in some cases, stop its progression. This drug combination has already been tested in adult patients with refractory tumors and seems to give encouraging results with stabilization of the tumor. The dose and toxicity of irinotecan and rapamycin are known when these drugs are administered separately and in a context different from that of refractory tumors. RAPIRI is a phase I clinical trial whose principal objectives are to determine the maximum dose at which these two molecules may be administered and to assess the safety of this new combination of drugs.

Conditions

Refractory Solid Tumors in Children

Outcome Measures

Primary Outcomes (2)

• Determine the maximum tolerated dose (MTD) of irinotecan and rapamycin combination in children with refractory solid tumors.

  The Dose-Limiting Toxicity (DLT) of the drug combination is determined during the first cycle (J1 to J28) of treatment. MTD will be defined as the dose level immediately below the dose level at which 2 patients in a cohort of 3 to 6 patients will have experienced a DLT.

  28 days

• Characterize the pharmacokinetics of rapamycin and irinotecan during the first cycle of treatment.

  Pharmacokinetic parameters for rapamycin will be evaluated at days 1 and 8 of the first cycle of treatment. Pharmacokinetic parameters for irinotecan will be evaluated at day 1 of the first cycle of treatment. Pharmacokinetic profile will be modelized for each patient.

  Day1 + day8

Study Arms (1)

rapamycin+irinotecan at a given dose

EXPERIMENTAL

Drug: Combined administration of irinotecan and rapamycin

Interventions

Combined administration of irinotecan and rapamycin DRUG

This phase I trial is a dose escalation study of irinotecan + rapamycin with a 3+3 statistical design.

rapamycin+irinotecan at a given dose

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \>= 1 year old and =\< 21 years old;
• Refractory solid tumors, histologically proven at diagnosis (no additional biopsy needs to be performed for the purpose of the study);
• Relapsed or refractory solid tumors after standard treatment or phase II, III-IV clinical trials treatment have failed;
• Karnofsky or Lansky status \>= 70%;
• Life expectancy \>= 8 weeks;
• No chemotherapy / radiotherapy within 4 weeks before entry into the study;
• Adequate biological parameters :
• Absolute neutrophil count \>= 1.0 x 109/L;
• Platelet count \>= 100 x 109/L;
• Hemoglobin \>= 8 mg/dL;
• Total bilirubine =\< 1.5 ULN;
• Transaminases =\< 2.5 ULN (=\< 5 ULN in case of liver metastases);
• Creatinine clearance (Cockroft) \>= 70 mL/min/1.73 m2;
• Normal coagulation profile with prothrombin \>= 70%, TCA =\< 35 and fibrinogen \>= 2 g/L;
• Patients with 1 to 3 previous therapeutic lines are eligible;

You may not qualify if:

• Patient with a constitutional anomaly of coagulation and/or of hemostasis (type hemophilia, von Willebrand disease, congenital clotting factor deficit, platelet disorder), exposing them to increased risk of bleeding;
• Pre-treatment with a mTOR inhibitor;
• Other simultaneous malignancy;
• Concurrent administration of any other anti-tumour therapy;
• Known hypersensitivity or contraindication to study drugs or ingredients;
• Severe concomitant disease (e.g. infection disease);
• Patient unable for medical follow-up;
• Pregnancy and/or lactation;
• Patient included in another clinical drug trial;
• Patient taking drugs interfering with pharmacology of rapamycin and/or irinotecan (e.g. drugs interfering with CYP3A4);
• Patient under judicial protection.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• University Hospital, Strasbourg, France: lead

Study Sites (9)

Hôpital des Enfants - Groupe Hospitalier Pellegrin

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Institut Hémato-Oncologie Pédiatrique (IHOP)

Lyon, 67008, France

Location

CHU La Timone

Marseille, 13005, France

Location

CHU Mère-Enfants

Nantes, 44093, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67098, France

Location

Hôpital des Enfants

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Jannier S, Kemmel V, Sebastia Sancho C, Chammas A, Sabo AN, Pencreach E, Farace F, Chenard MP, Lhermitte B, Geoerger B, Aerts I, Frappaz D, Leblond P, Andre N, Ducassou S, Corradini N, Bertozzi AI, Guerin E, Vincent F, Velten M, Entz-Werle N. SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers. Cancers (Basel). 2020 Oct 20;12(10):3051. doi: 10.3390/cancers12103051.

  PMID: 33092063 RESULT

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Natacha ENTZ-WERLE, MD, PhD

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2010
• First Posted: January 25, 2011
• Study Start: April 22, 2011
• Primary Completion: February 20, 2013
• Study Completion: February 20, 2013
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

FR (9)