Phase II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan
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
- 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,
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
24-week Overall Survival
The percentage of participants surviving 24 weeks from the start of study treatment
Annick Desjardins, MD, FRCPC
United States: Institutional Review Board
|Duke University Medical Center||Durham, North Carolina 27710|