Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy and Carmustine With or Without O6-Benzylguanine in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	SWOG-S0001 S0001, NCT00017147

Objectives

1. 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.
2. Compare the frequency and severity of toxic effects of these regimens in these patients.
3. Correlate the survival of these patients with the expression of O6-alkylguanine-DNA alkyltransferase.

Entry 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]

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 3,000/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Survival

Progression-free survival
Time to treatment failure
Toxicity

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.

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.

Quezado M, Ronchetti R, Rapkiewicz A, et al.: Chromogenic in situ hybridization accurately identifies EGFR amplification in small cell glioblastoma multiforme, a common subtype of primary GBM. Clin Neuropathol 24 (4): 163-9, 2005 Jul-Aug.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Deborah Blumenthal, MD, Study coordinator		Ph: 801-585-0211; 877-585-0303 Email: deborah.blumenthal@hsc.utah.edu
Alexander Spence, MD, Study coordinator		Ph: 206-543-0252 Email: aspence@u.washington.edu
Keith Stelzer, MD, PhD, Study coordinator		Ph: 541-296-7204

Registry Information
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
Trial Start Date		2001-09-01
Registered in ClinicalTrials.gov		NCT00017147
Date Submitted to PDQ		2001-04-09
Information Last Verified		2005-11-11
NCI Grant/Contract Number		CA32102