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S0001 RT and Carmustine With or Without O6BG in Patients With New Glioblastoma Multiforme or Gliosarcoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00017147
First received: June 6, 2001
Last updated: January 28, 2013
Last verified: January 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. O6-benzylguanine may help carmustine kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known whether radiation therapy and carmustine are more effective with or without O6-benzylguanine.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus carmustine with or without O6-benzylguanine in treating patients who have newly diagnosed glioblastoma multiforme or gliosarcoma.


Condition Intervention Phase
Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System
 Drug: carmustine
Radiation: radiation therapy
Drug: O6-Benzylguanine
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study of Radiation Therapy (RT) and O6-Benzylguanine (O6-BG) Plus BCNU Versus RT and BCNU Alone for Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Eye Cancer
Drug Information available for: Carmustine
U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Survival [ Time Frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5 ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5 ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: assessed weekly for 42 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 183
Study Start Date: September 2001
Study Completion Date: November 2012
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: O6-BG + BCNU + Radiation Therapy
O6-BG: 120 mg/m^2 IV over 1 hour on day 1 of each cycle BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose. Radiation Therapy: 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.
 Drug: carmustine

40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose for experimental arm with O6=BG.

200 mg/m^2 IV over 1 hour on day 2 of each cycle for the active comparator arm.

Radiation: radiation therapy
5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.
Drug: O6-Benzylguanine
120 mg/m^2 IV over 1 hour on day 1 of each cycle
Other Name: O6-BG
Active Comparator: BCNU + Radiation Therapy
BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle. Radiation Therapy: 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.
 Drug: carmustine

40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose for experimental arm with O6=BG.

200 mg/m^2 IV over 1 hour on day 2 of each cycle for the active comparator arm.

Radiation: radiation therapy
5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.

Detailed Description:

OBJECTIVES:

  • Compare the overall survival, failure-free survival, and progression-free survival of patients with newly diagnosed glioblastoma multiforme or gliosarcoma treated with radiotherapy and carmustine with or without O6-benzylguanine.
  • Compare the frequency and severity of toxic effects of these regimens in these patients.
  • Correlate the survival of these patients with the expression of O6-alkylguanine-DNA alkyltransferase.

OUTLINE: This is a randomized study. Patients are stratified according to age (under 50 vs 50 and over), prior surgery (biopsy only vs resection), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy daily 5 days a week over 7 weeks for a total of 34 fractions. Patients also receive chemotherapy comprising O6-benzylguanine IV over 1 hour followed 6 hours later by carmustine IV over 1 hour on day 1 of radiotherapy. Chemotherapy repeats every 6 weeks for a maximum of 7 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV as in arm I.

Patients are followed at week 48, every 4 months for 1 year, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study within 5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme or gliosarcoma

    • Biopsy or surgical resection within the past 28 days

      • MRI* with gadolinium performed before registration
      • Patients who undergo a simple biopsy only require preoperative MRI* with gadolinium
  • No more than 2 noncontiguous tumor sites based on T2-weighted MRI (in 3 dimensions)*
  • No prior radiotherapy-delivered cephalad to the interspace between the seventh cervical and the first thoracic vertebral body NOTE: *If an MRI is not medically feasible, patients may have a CT scan with contrast

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8 g/dL

Hepatic:

  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • SGOT/SGPT no greater than 2 times ULN
  • Alkaline phosphatase no greater than 2 times ULN
  • PT/PTT no greater than 1.2 times ULN

Renal:

  • Not specified

Cardiac:

  • No severe cardiac disease, including any of the following:

    • Uncontrolled arrhythmias or conduction defects
    • Major problems with edema (e.g., residual swelling in the legs from deep vein thrombosis)
    • Recent coronary artery disease
    • Poorly controlled hypertension (i.e., diastolic blood pressure greater than 110 mm Hg and/or systolic blood pressure greater than 180 mm Hg)

Pulmonary:

  • DLCO at least 70% of predicted
  • No severe pulmonary disease

Other:

  • HIV negative
  • No severe Cushing's syndrome
  • No known allergies to any of the study drugs
  • No major psychiatric illness
  • No poorly controlled diabetes complicated by steroid treatment
  • No other medical illness that cannot be adequately controlled or that would preclude study participation
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy
  • No other concurrent antitumor chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy except postmenopausal estrogen replacement therapy
  • Corticosteroids at stable or decreasing dose for tumor edema allowed

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy
  • No other concurrent radiotherapy (including intensity-modulated radiotherapy) to the index lesion(s)

Surgery:

  • See Disease Characteristics
  • No concurrent antitumor surgery

Other:

  • No other concurrent investigational drugs
  • No other concurrent antineoplastic drugs or therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00017147

  Show 163 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Deborah T. Blumenthal, MD University of Utah
Study Chair: Alexander M. Spence, MD University of Washington
Study Chair: Keith J. Stelzer, MD, PhD Celilo Cancer Center at Mid-Columbia Medical Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Blumenthal DT, Wade M, Rankin CJ, et al.: MGMT methylation in newly-diagnosed glioblastoma multiforme (GBM): from the S0001 phase III study of radiation therapy (RT) and O6-benzylguanine, (O6BG) plus BCNU versus RT and BCNU alone for newly diagnosed GBM. [Abstract] J Clin Oncol 24 (Suppl 18): A-1512, 2006.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00017147     History of Changes
Other Study ID Numbers: CDR0000068656, S0001, U10CA032102
Study First Received: June 6, 2001
Last Updated: January 28, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Neoplasms
Eye Neoplasms
Glioblastoma
Gliosarcoma
Neoplasms by Site
Eye Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
 Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carmustine
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013