Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors
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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 |
- 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 ]
- 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) |
-
Drug: Bevacizumab
Eligibility| Ages Eligible for Study: | 18 Months to 23 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Stacie Stapleton, MD | 727-767-4176 | Stacie.Stapleton@allkids.org |
| Contact: Frances Hamblin, RN | 727-767-2423 | Frances.Hamblin@allkids.org |
| 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 | |
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 May 23, 2013