A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan|
- 24-week Overall Survival [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]The percentage of participants surviving 24 weeks from the start of study treatment
- 24-week Progression-free Survival (PFS) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]The percentage of participants surviving 24 weeks from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.
- Median Progression-free Survival (PFS) [ Time Frame: Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 47 months ] [ Designated as safety issue: No ]Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
- Median Overall Survival (OS) [ Time Frame: Time in months from the start of study treatment to date of death due to any cause, assessed up to 47 months ] [ Designated as safety issue: No ]Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
- Incidence and Severity of Central Nervous System (CNS) Hemorrhage [ Time Frame: 47 months ] [ Designated as safety issue: Yes ]Incidence and severity of CNS hemorrhage
- Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities [ Time Frame: 47 months ] [ Designated as safety issue: Yes ]Incidence of grade ≥ 4 hematologic and ≥ grade 3 non-hematologic toxicities
|Study Start Date:||December 2008|
|Study Completion Date:||October 2012|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00735436
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD, FRCPC||Duke University|