Clinical trial NCT01282697: Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients With Refractory Solid Tumors
Official title: Phase I Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients With Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Refractory Solid Tumors in Children
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
Collaborators: name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2011-01-25
Enrollment: 42
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Determine the maximum tolerated dose (MTD) of irinotecan and rapamycin combination in children with refractory solid tumors.
timeFrame: 28 days
measure: Characterize the pharmacokinetics of rapamycin and irinotecan during the first cycle of treatment.
timeFrame: Day1 + day8
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital des Enfants - Groupe Hospitalier Pellegrin
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Institut Hémato-Oncologie Pédiatrique (IHOP)
city: Marseille
country: France
facility: CHU La Timone
city: Nantes
country: France
facility: CHU Mère-Enfants
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Hôpital des Enfants
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Hôpitaux Universitaires de Strasbourg
name: Natacha ENTZ-WERLE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: