Clinical trial NCT00735436
Conditions: Malignant Glioma Glioblastoma Multiforme Gliosarcoma
Keywords: Malignant glioma Glioblastoma multiforme GBM Gliosarcoma Gliadel Carmustine Irinotecan CPT-11 Camptosar Avastin Bevacizumab
Sponsor: Duke University
Start date: 2008-12-01; Completion date: 2012-10-01
Enrollment: 18 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. The secondary objectives are to determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and irinotecan.

Detailed description:
This is a phase II study of the combination of Gliadel followed by Avastin and irinotecan in grade IV malignant glioma patients. The study will have survival and toxicity endpoints. Subjects will be identified by the investigator as those patients who have histologically documented grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with recurrent or progressive disease who are able to undergo a gross total resection (GTR).

Part I: Gliadel wafer- 1-8 wafers inserted at time of gross total resection. Treatment cycle is 42 days in length. For patients with ≥ Grade 1 toxicity will allow 84 days prior to beginning therapy with Avastin and Irinotecan (CPT-11).

Part II: Avastin Plus Irinotecan (Cycles 1-12) consists of the following (cycle length is 6 weeks):

* Irinotecan 125 mg/m2 (not taking enzyme-inducing anti-epileptic drugs (EIAEDs)) or 340 mg/m2 (taking EIAEDs) given every two weeks on days 1, 15, 29, etc.;
* If the patient has the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction; For patients on an EIAED, the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2;
* Avastin 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29, etc.

The primary objective of this phase II study is to determine whether the administration of Gliadel wafers followed by Avastin and irinotecan to patients with recurrent GBM is a treatment regimen worthy of further investigation in a randomized clinical trial. The basis for making this decision will be the proportion of patients who survive at least 24 weeks after initiation of protocol treatment.

In the initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The two major toxicities associated with irinotecan are myelosuppression and diarrhea. Side effects associated with Gliadel are seizures, brain edema (swelling), healing abnormalities, wound infection and body pain.

Arms: arm 1: Gliadel/Avastin/CPT-11
Interventions: intervention 1: Gliadel/Avastin/CPT-11
Intervention descriptions: intervention 1: None

Protocol documents: