Symptoms and General Pathology

All Conditions

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Irinotecan

Temozolomide

Vincristine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level 1.5\* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

\* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2

Rajkumar Venkatramani, MD

This phase I study is designed to determine the maximum tolerated dose of Irinotecan given intravenous for 5 days every 3 weeks in combination with fixed doses of Vincristine, Temozolomide and Bevacizumab (VIT-B) in patients with refractory solid tumors.

A Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin

A Phase I Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin

Number of participants with dose limiting toxicity events

Children's Hospital Los Angeles

Medical Staff/USC Faculty CWR

combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5

Dose Level 1

combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5

Dose Level 2

Dose Level 1, 2

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Rajkumar Venkatramani

combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1

Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5

Dose Level 1.5\* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5

Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5

Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5

\* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed

Single Arm

Dose Limiting Toxicity

Irinotecan 30 mg

Irinotecan 50 mg

Anti-Infective Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

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

Combined administration of irinotecan and rapamycin

Natacha ENTZ-WERLE, MD, PhD

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.

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

Phase I Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients 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.

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.

Gustave Roussy, Cancer Campus, Grand Paris

University Hospital, Strasbourg, France

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin	NCT00993044	Refractory Soli...	Irinotecan Vincristine Temozolomide Bevacizumab	12 Months - 20 Years	Children's Hospital Los Angeles
Clinical Trial of Rapamycin and Irinotecan in Pediatric Patients With Refractory Solid Tumors	NCT01282697	Refractory Soli...	Combined admini...	1 Year - 21 Years	University Hospital, Strasbourg, France
A Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin	NCT00993044	Refractory Soli...	Irinotecan Vincristine Temozolomide Bevacizumab	12 Months - 20 Years	Children's Hospital Los Angeles
A Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin	NCT00993044	Refractory Soli...	Irinotecan Vincristine Temozolomide Bevacizumab	12 Months - 20 Years	Children's Hospital Los Angeles

Spots Global Cancer Trial Database for refractory solid tumors in children