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

NCT ID: NCT01282697

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-22
• Study Completion Date: 2013-02-20

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rapamycin+irinotecan at a given dose

Group Type: EXPERIMENTAL

Combined administration of irinotecan and rapamycin

Intervention Type: DRUG

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

Interventions

Combined administration of irinotecan and rapamycin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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;
• No current grade >= 2 organ toxicity based on NCI-CTCAE version 3.0;
• All patients with reproductive potential must have an effective method of birth control while on study;
• Negative pregnancy test in females when indicated;
• Informed written consent signed by patients or their parents or legal guardians;
• Patient who was informed of the results of prior medical consultation;
• Patient having a social insurance.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: collaborator

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Natacha ENTZ-WERLE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpitaux Universitaires de Strasbourg

Locations

Hôpital des Enfants - Groupe Hospitalier Pellegrin

Bordeaux, , France

Centre Oscar Lambret

Lille, , France

Institut Hémato-Oncologie Pédiatrique (IHOP)

Lyon, , France

CHU La Timone

Marseille, , France

CHU Mère-Enfants

Nantes, , France

Institut Curie

Paris, , France

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Hôpital des Enfants

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 33092063 (View on PubMed)

Other Identifiers

4791

Identifier Type: -

Identifier Source: org_study_id