Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by All Children’s Hospital Johns Hopkins Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
V Foundation
Information provided by:
All Children’s Hospital Johns Hopkins Medicine
ClinicalTrials.gov Identifier:
NCT00876993
First received: April 6, 2009
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.


Condition Intervention Phase
Central Nervous System Tumors
Drug: Bevacizumab
Drug: Irinotecan
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors

Resource links provided by NLM:


Further study details as provided by All Children’s Hospital Johns Hopkins Medicine:

Primary Outcome Measures:
  • To conduct a phase I study to evaluate the safety of this combination of chemotherapy agents. [ Time Frame: Every 2 months (every 2 cycles) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the response of children with recurrent or refractory central nervous system tumors with this combination of chemotherapy agents. [ Time Frame: Every 2 months (Every 2 cycles) ] [ Designated as safety issue: No ]
  • To compare the response and toxicity with historical controls with the same disease. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To estimate the 2 and 5 year survival with children treated with this regimen. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To provide safety and efficacy data for to recommend further larger studies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2008
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bevacizumab
    Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
    Drug: Irinotecan
    Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
    Drug: Temozolomide
    For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course. Doses will be escalated according to standard phase I dose escalation criteria. Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
  Eligibility

Ages Eligible for Study:   18 Months to 23 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
  • The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
  • Age 18 months though age 23 years are eligible for this protocol.
  • The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
  • Bone marrow should be recovered from prior therapy with ANC >1500 and platelets >100,000.
  • Serum creatinine should be less than institutional upper limit of norm.
  • ALT/AST <3 times normal and bilirubin <1.5 times normal.
  • Neurologic symptoms should be stable for 1 week with stable or decreasing doses of steroids.
  • Patients should not be pregnant or breast feeding.

Exclusion Criteria:

  • Patients with bleeding disorders or on anticoagulants.
  • Uncontrolled hypertension.
  • Other risks of bleeding determined on individual basis.
  • Patients receiving enzyme inducing anticonvulsants.
  • Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
  • For patients receiving bevacizumab, those who have had surgical procedures should not receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines are not considered minor procedures and may occur at any time prior to or during therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00876993

Contacts
Contact: Stacie Stapleton, MD 727-767-4176 Stacie.Stapleton@allkids.org
Contact: Frances Hamblin, RN 727-767-2423 Frances.Hamblin@allkids.org

Locations
United States, Florida
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Stacie Stapleton, MD    727-767-4176    Stacie.Stapleton@allkids.org   
Contact: Frances Hamblin, RN    727-767-2423    Frances.Hamblin@allkids.org   
Sub-Investigator: Jerry Barbosa, MD         
Sub-Investigator: Irmel Ayala, MD         
Sub-Investigator: Nanette Grana, MD         
Sub-Investigator: Kelly Sawczyn, MD         
Sub-Investigator: Cynthia Guerra, ARNP         
Sub-Investigator: Claudia Lukas, PA-C         
Sub-Investigator: Sonja Steinbrueck, RN         
Sub-Investigator: Frances Hamblin, RN         
Sub-Investigator: Gregory Hale, MD         
Sponsors and Collaborators
All Children’s Hospital Johns Hopkins Medicine
V Foundation
  More Information

No publications provided

Responsible Party: Stacie Stapleton, MD, All Children's Hospital
ClinicalTrials.gov Identifier: NCT00876993     History of Changes
Other Study ID Numbers: ACH-CNS-001
Study First Received: April 6, 2009
Last Updated: June 27, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Temozolomide
Dacarbazine
Irinotecan
Bevacizumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
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 April 16, 2014