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

NCT01186406 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00025180
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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

Keywords

glioblastoma multiforme; gliosarcoma; malignant glioma; glioma; Gliadel; carmustine wafers; Avastin; bevacizumab; Temodar; temozolomide; Pro00025180; Desjardins; Duke; Preston Robert Tisch Brain Tumor Center

Outcome Measures

Primary Outcomes (1)

• 21-month Overall Survival

  The percentage of participants alive at 21 months after the start of study treatment. Overall survival was calculated from the date study treatment started until the date of death or the date of last follow-up if alive. Kaplan-Meier methods were used to estimate overall survival.

  21 months

Secondary Outcomes (3)

• Median Overall Survival

  21 months

• Median Progression-free Survival

  21 months

• Unacceptable Toxicity Related to the Treatment Regimen

  27 months

Study Arms (1)

Gliadel, Radiation Therapy, Avastin, Temodar

EXPERIMENTAL

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

Drug: Gliadel; Radiation: Radiation Therapy; Drug: Avastin; Drug: Temodar

Interventions

Gliadel DRUG

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

Also known as: Gliadel (carmustine wafers)

Gliadel, Radiation Therapy, Avastin, Temodar

Radiation Therapy RADIATION

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

Gliadel, Radiation Therapy, Avastin, Temodar

Avastin 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.

Also known as: Avastin (bevacizumab)

Gliadel, Radiation Therapy, Avastin, Temodar

Temodar 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).

Also known as: Temodar (temozolomide)

Gliadel, Radiation Therapy, Avastin, Temodar

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Cancer Center

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma

Interventions

carmustine, poliferprosan 20 drug combination; Carmustine; Radiotherapy; Bevacizumab; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Annick Desjardins, MD, FRCPC
• Organization: Duke University Medical Center

annick.desjardins@duke.edu

9196846173

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2010
• First Posted: August 23, 2010
• Study Start: April 1, 2011
• Primary Completion: June 16, 2014
• Study Completion: June 16, 2014
• Last Updated: February 15, 2019
• Results First Posted: October 22, 2014

Record last verified: 2019-01

Locations

US (1)