Trial record 1 of 1 for:    RTOG 0825
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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

April 18, 2009
June 9, 2014
April 2009
July 2013   (final data collection date for primary outcome measure)
  • 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).
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00884741 on ClinicalTrials.gov Archive Site
  • 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.
Treatment-related toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma
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

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.

PRIMARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to temozolomide and radiotherapy improves efficacy, as measured by progression-free (PFS) and/or overall survival (OS), in patients with newly diagnosed glioblastoma. (Gliosarcoma closed to accrual as of 07/13/10).

II. To assess the association between overall survival and K^trans change from T1 to T2.

III. To assess the association between OS and spin echo CBV change from T1 to T2.

SECONDARY OBJECTIVES:

I. To determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit from the addition of bevacizumab to temozolomide and radiotherapy, as measured by OS or PFS, in these patients.

II. To compare the toxicities of chemoradiotherapy with bevacizumab vs conventional chemoradiotherapy in these patients.

III. To assess the association between PFS and K^trans change from T1 to T2. IV. To assess the association between PFS and spin echo CBV change from T1 to T2.

V. To assess the association between values of K^trans and spin echo CBV measured separately at T0 and at T1, and OS and PFS.

VI. To assess the association between OS and K^trans changes from T0 to T1 and from T2 to T3.

VII. To assess the association between OS and spin echo CBV changes from T0 to T1 and from T2 to T3.

VIII. To assess the association between OS and apparent diffusion coefficient (ADC) change from T0 to T1.

IX. To assess the association between OS and ADC change from T1 to T2. X. To assess the association between PFS and ADC change from T0 to T1. XI. To assess the association between PFS and ADC change from T1 to T2. XII. To assess the association between T1 values of ADC and OS and PFS. XIII. To assess the association between change in lesion size between T1 and T3, as measured by advanced MRI, and OS and PFS.

TERTIARY OBJECTIVES:

I. To determine the differential acute effects associated with the addition of bevacizumab to temozolomide and radiation, as compared to the conventional arm, on measures of neurocognitive function (NCF), health-related quality of life (HR-QOL), and symptoms during radiation and across the longitudinal progression-free interval.

II. To determine the relationship of NCF, HR-QOL, and symptoms, with PFS and OS.

III. To determine the association between tumor molecular profile (i.e., mesenchymal/angiogenic phenotype and proneural phenotype) and NCF, HR-QOL, and symptoms.

IV. To describe the association between HR-QOL as measured by the EORTC-QL30/BCM20 and mean symptom severity as measured by the MDASI-BT in patients enrolled in this study.

V. To evaluate the relationship between self-reported NCF and objectively measured tests of NCF.

VI. To assess the association between measures of change in enhancing tumor size at week 22 and OS in patients treated with chemoradiotherapy with and without bevacizumab.

VII. To assess the association between measures of change in T2-based tumor size at week 22 and OS in patients treated with these regimens.

VIII. To assess the association between changes in ADC values and OS in patients treated with these regimens.

IX. To assess the association between measures of change in enhancing tumor size at week 22 and OS in patients with glioma receiving chemoradiotherapy with and without bevacizumab.

X. To assess the association between measures of change in T2-based tumor size at week 22 and OS in patients with glioma receiving chemoradiotherapy with and without bevacizumab.

XI. To assess the association between changes in ADC values and OS in patients with glioma receiving chemoradiotherapy with and without bevacizumab.

OUTLINE: This is a multicenter study. Patients are stratified according to MGMT methylation status (methylated vs unmethylated vs invalid) and tumor molecular profile metagene score (favorable vs unfavorable vs undetermined). Patients are randomized to 1 of 2 treatment arms.

ARM I: 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.

ARM II: 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.

Some patients may undergo Dynamic Susceptibility-Contrast MRI (DSC-MRI) and Dynamic Contrast-Enhanced (DCE-MRI) imaging at baseline, periodically during the study, and after completion of treatment.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • 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
  • 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.
    Interventions:
    • Drug: temozolomide
    • Other: placebo
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
    • Procedure: 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.
    Interventions:
    • Drug: temozolomide
    • Biological: bevacizumab
    • Other: placebo
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
    • Procedure: quality-of-life assessment
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
897
Not Provided
July 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00884741
NCI-2009-01670, NCI-2009-01670, RTOG-0825, CDR0000640428, RTOG 0825, RTOG-0825, U10CA021661
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mark Gilbert Radiation Therapy Oncology Group
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP