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

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.