Trial record 14 of 26 for:    United States, Indiana | Community Regional Cancer Care

Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00884741
First received: April 18, 2009
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial is studying temozolomide and radiation therapy to compare how well they work when given together with or without bevacizumab in treating patients with newly diagnosed glioblastoma. (gliosarcoma closed to accrual as of 07-13-10). Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Drug: temozolomide
Biological: bevacizumab
Other: placebo
Radiation: radiation therapy
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase III Double-Blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: From randomization to the date of death due to any cause or otherwise, the last follow-up date on which the patient was reported alive, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and differences between treatment arms will be tested in the log rank test (Mantel 1966).

  • Progression-free survival [ Time Frame: From randomization to the date of first progression or death or, otherwise, the last follow-up date on which the patient was reported alive, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and differences between treatment arms will be tested in the log rank test (Mantel 1966).


Secondary Outcome Measures:
  • Treatment-related toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Differences in observed severities of toxicities (grade 3+) between groups will be tested using a chi square test.

  • Molecular profile [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Multivariate analysis will be performed using the Cox proportional hazard model for both outcomes to determine if molecular profile is an independent prognostic factor and possibly a predictive factor for the use of bevacizumab.


Enrollment: 897
Study Start Date: April 2009
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (radiotherapy, temozolomide, placebo)
Patients undergo radiotherapy (intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy) once daily 5 days a week for 6 weeks and receive concurrent oral temozolomide once daily for up to 7 weeks. Beginning 4 weeks after completion of chemoradiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Other: placebo
Given IV
Other Name: PLCB
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (radiotherapy, temozolomide, bevacizumab)
Patients undergo chemoradiotherapy and receive adjuvant temozolomide as in arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: placebo
Given IV
Other Name: PLCB
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed glioblastoma (gliosarcoma closed to accrual as of 07-13-10)

    • WHO grade IV disease
    • Tumor must have a supratentorial component
  • Has undergone partial or complete surgical resection of tumor within the past 3-5 weeks

    • Diagnosis must be made by surgical excision (not by stereotactic biopsy)
    • No significant postoperative hemorrhage, defined as > 1 cm diameter of blood in the tumor cavity by MRI or CT scan
  • Has ≥ 1 block of tumor tissue of sufficient size available for analysis of MGMT status and determination of molecular profile

    • At least 1 cm³ of tissue composed primarily of tumor must be present
    • No CUSA (Cavitron ultrasonic aspirator)-derived material
  • No recurrent or multifocal malignant glioma
  • No metastases detected below the tentorium or beyond the cranial vault
  • Karnofsky performance status 70-100%
  • Absolute neutrophil count ≥ 1,800/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
  • ALT and AST ≤ 3 times normal
  • Bilirubin ≤ 2.0 mg/dL
  • PT/INR < 1.4 (for patients not on warfarin)
  • Creatinine ≤ 1.7 mg/dL
  • Urine protein: creatinine ratio < 0.5 OR 24-hour urine protein < 1,000 mg
  • BUN ≤ 30 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • Systolic blood pressure (BP) ≤ 160 mm Hg or diastolic BP ≤ 90 mm Hg
  • No evidence of acute cardiac ischemia by electrocardiogram
  • No other invasive malignancy within the past 3 years, except for nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
  • No severe, active comorbidity, including any of the following:

    • Unstable angina and/or congestive heart failure within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Evidence of recent myocardial infarction or ischemia as indicated by ST elevations of ≥ 2 mm by EKG
    • New York Heart Association class II-IV congestive heart failure requiring hospitalization within the past 12 months
    • Stroke, cerebral vascular accident, or transient ischemic attack within the past 6 months
    • Serious, inadequately controlled cardiac arrhythmia
    • Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection) or clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Serious or non-healing wound, ulcer, or bone fracture
    • Abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or significant traumatic injury within the past 28 days
    • Acute bacterial or fungal infection requiring IV antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS based on current CDC definition
    • Active connective tissue disorders (e.g., lupus or scleroderma) that, in the opinion of the treating physician, may place the patient at high risk for radiation toxicity
    • Any other major medical illness or psychiatric impairment that, in the opinion of the investigator, would preclude study drug administration or completion of study therapy
  • Recovered from prior surgery
  • No prior chemotherapy or radiosensitizers for cancer of the head and neck region

    • Prior chemotherapy for a different cancer is allowed
  • No prior temozolomide or bevacizumab
  • No prior Gliadel wafers or any other intratumoral or intracavitary treatment
  • No prior radiotherapy to the head and neck (except for T1 glottic cancer) resulting in overlap of radiotherapy fields
  • More than 28 days since prior major surgical procedure or open biopsy other than craniotomy for tumor resection
  • More than 30 days since prior and no concurrent treatment on another therapeutic clinical trial
  • No concurrent growth factors to induce elevations in neutrophil count for the purposes of administration of temozolomide on the scheduled dosing interval; to allow treatment with temozolomide at a higher dose; or to avoid interruption of the treatment during concurrent radiotherapy
  • No concurrent erythropoietin
  • No concurrent tumor debulking surgery, other chemotherapy, immunotherapy, biologic therapy, or additional stereotactic boost radiotherapy
  • No other concurrent investigational drugs during the "blinded phase" of the study
  • Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin) allowed provided both of the following criteria are met:

    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
    • In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  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: NCT00884741

  Show 289 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Gilbert Radiation Therapy Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00884741     History of Changes
Other Study ID Numbers: NCI-2009-01670, NCI-2009-01670, RTOG-0825, CDR0000640428, RTOG 0825, RTOG-0825, U10CA021661
Study First Received: April 18, 2009
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 28, 2014