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 (VIT-B)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rajkumar Venkatramani, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00993044
First received: October 8, 2009
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Refractory Solid Tumors in Children
Drug: Irinotecan
Drug: Vincristine
Drug: Temozolomide
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Dose Limiting Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Number of participants with dose limiting toxicity events


Enrollment: 13
Study Start Date: September 2009
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: Irinotecan

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

Drug: Vincristine

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

Drug: Temozolomide

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

Drug: Bevacizumab

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


  Eligibility

Ages Eligible for Study:   12 Months to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: Patients must be > 12 months and < 21 years of age at the time of study entry.
  • Weight: Patient must be more than or equal to 10 Kilograms.

Histological Diagnosis:

  • Patients must have had histological verification of the malignancy at some time prior to study entry.
  • All solid tumors are eligible with the exclusion of lymphomas. For patients with neuroblastoma, diagnosis based on elevated catecholamines in the urine and tumor cells on bone marrow aspirates/biopsies is acceptable.
  • For patients with germ cell tumors, diagnosis based on elevated tumor markers (serum alpha fetoprotein and/or serum beta human chorionic gonadotropin) and radiographic evidence of disease is acceptable.

Disease Status:

  • Disease must have failed standard therapy (therapies) or be a disease for which no standard therapy exists.
  • Patient with stable disease on other therapies are not eligible.

Performance Level:

  • Karnofsky > 50% for patients >16 years of age and Lansky > 50 for children < 16 years of age (Appendix I).
  • Life Expectancy: Must be > 8 weeks.

Exclusion Criteria:

  • Patients who have received bevacizumab and/or Irinotecan previously are ineligible. Non brain tumor patients who have previously received Temozolomide are ineligible.
  • Pregnancy or Breast-Feeding: Pregnant patients are ineligible for this study due to the known teratogenic effects of the cytotoxic agents. Pregnancy tests must be obtained in females of childbearing potential prior to enrollment.
  • Lactating women must agree not to breast-feed.
  • Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
  • Patients Who Have an Uncontrolled Infection will not be eligible for enrollment until all infections are under control.
  • Clinically Significant Unrelated Systemic Illness: Patients with serious infections or significant pulmonary, hepatic, renal, or other end-organ dysfunction which in the judgment of the Principal or Co-Investigators would compromise the patient's ability to tolerate prescribed chemotherapy or are likely to interfere with the study procedures or results will not be eligible.
  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: NCT00993044

Locations
United States, California
Childrens Hospital los Angeles
Los angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Principal Investigator: Rajkumar Venkatramani, MD Children's Hospital Los Angeles
  More Information

Publications:
Responsible Party: Rajkumar Venkatramani, Assistant Professor of Pediatrics, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT00993044     History of Changes
Other Study ID Numbers: 09-00214
Study First Received: October 8, 2009
Results First Received: January 3, 2014
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Vincristine
Irinotecan
Temozolomide
Bevacizumab
Dacarbazine
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014