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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
Eisai Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01186406
First received: August 19, 2010
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Gliosarcoma
Drug: Gliadel
Radiation: Radiation Therapy
Drug: Avastin
Drug: Temodar
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 21-month Overall Survival [ Time Frame: 21 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Median Overall Survival [ Time Frame: 21 months ] [ Designated as safety issue: No ]
    Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival.

  • Median Progression-free Survival [ Time Frame: 21 months ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time in months from the date study treatment started until the date of progression or the date of death if death occurred before progression, or until the date of last follow-up if alive without progression. Kaplan-Meier methods were used to estimate progression-free survival.

  • Unacceptable Toxicity Related to the Treatment Regimen [ Time Frame: 27 months ] [ Designated as safety issue: Yes ]
    The number of patients experiencing unacceptable toxicity defined as the occurrence of ≥ grade 2 CNS hemorrhage or treatment-related grade 4 or 5 non-hematologic toxicity.


Enrollment: 41
Study Start Date: April 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Gliadel
Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection.
Other Name: Gliadel (carmustine wafers)
Radiation: Radiation Therapy
At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy.
Drug: 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.

Other Name: Avastin (bevacizumab)
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).
Other Name: Temodar (temozolomide)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01186406

Locations
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Genentech, Inc.
Eisai Inc.
Investigators
Principal Investigator: Annick Desjardins, MD, FRCPC Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01186406     History of Changes
Other Study ID Numbers: Pro00025180
Study First Received: August 19, 2010
Results First Received: October 17, 2014
Last Updated: October 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
glioblastoma multiforme
gliosarcoma
malignant glioma
glioma
Gliadel
carmustine wafers
Avastin
bevacizumab
Temodar
temozolomide
Pro00025180
Desjardins
Duke
Preston Robert Tisch Brain Tumor Center

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Carmustine
Temozolomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014