Clinical trial NCT01186406: Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)
Official title: Phase II Trial for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Concurrent Radiation Therapy, Temodar and Avastin, Then Followed by Avastin and Temodar Post-Radiation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Gliosarcoma
Keywords: glioblastoma multiforme
gliosarcoma
malignant glioma
glioma
Gliadel
carmustine wafers
Avastin
bevacizumab
Temodar
temozolomide
Pro00025180
Desjardins
Duke
Preston Robert Tisch Brain Tumor Center
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Eisai Inc.
First posted: 2010-08-23
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of Gliadel wafers at the time of surgery, followed by the combination of radiation, Temodar, and Avastin, and then the combination of Avastin and Temodar, after radiation is complete, on malignant brain tumors.

About six weeks after surgery, subjects will begin standard radiation therapy, a fixed dose of Avastin every 2 weeks, and daily Temodar for the six and a half weeks of radiation. Beginning 2-3 weeks after the last radiation therapy, subjects will be given the same fixed dose of Avastin intravenously (through the vein) every 14 days. They will also be given a higher dose of oral Temodar to take daily the first 5 days of each 28-day study cycle.


Eligibility criteria: Inclusion Criteria:

* Patients must have a MRI consistent with a WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma), and be candidates for surgical resection with Gliadel wafer placement. Patients have to be within 6 weeks of the last major surgical procedure.
* Age ≥ 18 years
* Candidates for Gliadel
* If a prior procedure was done, an interval of at least 2 weeks and not \> 8 weeks between prior major surgical procedure and study enrollment
* No prior radiotherapy or chemotherapy for a brain tumor
* Karnofsky \> 60%
* Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/microliters, platelets ≥ 125,000 cells/microliters
* Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal.
* Signed informed consent approved by the Institutional Review Board
* If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards as stated in the informed consent.

Exclusion Criteria:

* Pregnancy or breast feeding.
* Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
* Active infection requiring IV antibiotics.
* Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
* Evidence of \> grade 1 CNS hemorrhage on baseline MRI or CT scan.
* Prior treatment with Avastin for any condition
* Prior, unrelated malignancy requiring active treatment with the exception cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin

Avastin-Specific Exclusion Criteria:

* Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to study enrollment
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrollment
* History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to study enrollment
* Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first Avastin infusion or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
* History of abdominal fistula, gastrointestinal perforation within 6 months prior to study enrollment
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of Avastin
* Pregnant (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential

Primary outcomes:
measure: 21-month Overall Survival
timeFrame: 21 months
Secondary outcomes:
measure: Median Overall Survival
timeFrame: 21 months
measure: Median Progression-free Survival
timeFrame: 21 months
measure: Unacceptable Toxicity Related to the Treatment Regimen
timeFrame: 27 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: The Preston Robert Tisch Brain Tumor Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Annick Desjardins, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: