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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2011 by University Hospital, Strasbourg, France
Sponsor:
Collaborator:
Gustave Roussy, Cancer Campus, Grand Paris
Information provided by:
University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier:
NCT01282697
First received: November 12, 2010
Last updated: January 24, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Refractory Solid Tumors in Children
Drug: Combined administration of irinotecan and rapamycin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by University Hospital, Strasbourg, France:

Primary Outcome Measures:
  • Determine the maximum tolerated dose (MTD) of irinotecan and rapamycin combination in children with refractory solid tumors. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.

  • Characterize the pharmacokinetics of rapamycin and irinotecan during the first cycle of treatment. [ Time Frame: Day1 + day8 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 33
Study Start Date: February 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rapamycin+irinotecan at a given dose Drug: Combined administration of irinotecan and rapamycin
This phase I trial is a dose escalation study of irinotecan + rapamycin with a 3+3 statistical design.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01282697

Contacts
Contact: Natacha ENTZ-WERLE, MD, PhD 33(0)388128091 Natacha.entz-werle@chru-strasbourg.fr
Contact: Erwan PENCREACH, PharmD, PhD 33(0)388127179 Erwan.pencreach@chru-strasbourg.fr

Locations
France
Hôpital des Enfants - Groupe Hospitalier Pellegrin Not yet recruiting
Bordeaux, France, 33076
Contact: Yves PEREL, MD, PhD         
Principal Investigator: Yves PEREL, MD, PhD         
Centre Oscar Lambret Not yet recruiting
Lille, France, 59020
Contact: Pierre LEBLOND, MD         
Principal Investigator: Pierre LEBLOND, MD         
Institut Hémato-Oncologie Pédiatrique (IHOP) Not yet recruiting
Lyon, France, 67008
Contact: Didier FRAPPAZ, MD         
Principal Investigator: Didier FRAPPAZ, MD         
CHU La Timone Not yet recruiting
Marseille, France, 13005
Contact: Nicolas ANDRE, MD         
Principal Investigator: Nicolas ANDRE         
CHU Mère-Enfants Not yet recruiting
Nantes, France, 44093
Contact: Nadège CORRADINI, MD         
Principal Investigator: Nadège CORRADINI, MD         
Institut Curie Not yet recruiting
Paris, France, 75005
Contact: Isabelle AERTS, MD         
Principal Investigator: Isabelle AERTS, MD         
Hôpitaux Universitaires de Strasbourg Not yet recruiting
Strasbourg, France, 67098
Contact: Natacha ENTZ-WERLE, MD, PhD         
Principal Investigator: Natacha ENTZ-WERLE, MD, PhD         
Hôpital des Enfants Not yet recruiting
Toulouse, France, 31059
Contact: Hervé RUBIE, MD         
Principal Investigator: Hervé RUBIE, MD         
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Birgit GEOERGER, MD         
Principal Investigator: Birgit GEOERGER, MD         
Sponsors and Collaborators
University Hospital, Strasbourg, France
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
Principal Investigator: Natacha ENTZ-WERLE, MD, PhD Hôpitaux Universitaires de Strasbourg
  More Information

No publications provided

Responsible Party: Christine GEILLER, Direction de la Recherche Clinique et des Innovations - Hôpitaux Universitaires de Strasbourg
ClinicalTrials.gov Identifier: NCT01282697     History of Changes
Other Study ID Numbers: 4791
Study First Received: November 12, 2010
Last Updated: January 24, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Irinotecan
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014