Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)

NCT ID: NCT01186406

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-06-16

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.

Conditions

Glioblastoma Multiforme; Gliosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gliadel, Radiation Therapy, Avastin, Temodar

Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation

Group Type: EXPERIMENTAL

Gliadel

Intervention Type: DRUG

Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection.

Radiation Therapy

Intervention Type: RADIATION

At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy.

Avastin

Intervention Type: DRUG

Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively.

Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days.

Temodar

Intervention Type: DRUG

At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation. In addition, beginning 2-3 weeks after the last radiation therapy, but not greater than 8 weeks, patients will be treated with 5 day Temodar (200 mg/ m2).

Interventions

Gliadel

Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection.

Intervention Type: DRUG

Radiation Therapy

At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy.

Intervention Type: RADIATION

Avastin

Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively.

Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days.

Intervention Type: DRUG

Temodar

At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation. In addition, beginning 2-3 weeks after the last radiation therapy, but not greater than 8 weeks, patients will be treated with 5 day Temodar (200 mg/ m2).

Intervention Type: DRUG

Other Intervention Names

Gliadel (carmustine wafers); Avastin (bevacizumab); Temodar (temozolomide)

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Annick Desjardins, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, United States

Countries

United States

Related Links

http://www.cancer.duke.edu/btc/

The Preston Robert Tisch Cancer Center

Other Identifiers

Pro00025180

Identifier Type: -

Identifier Source: org_study_id