Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 18 and over NCI SWOG-8737 INT-0093

Objectives

I.  Compare survival time and time to progression in adults with high-grade 
supratentorial gliomas randomly assigned to treatment with 24-hour infusional 
diaziquone vs. carmustine.
II.  Compare the PR and CR rates in these two treatment groups.
III.  Develop a data base on current surgical practices with protocol patients.
IV.  Study further the prevalence and management of pulmonary toxicity 
associated with BCNU administration.
V.  Correlate clinical outcome with residual tumor volume at entry.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients aged 18 years and older with 
histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma 
multiforme (Kernohan's Grade III or IV astrocytoma).  Eligible patients 
include both newly diagnosed patients (having completed all anticipated 
surgical procedures and who have either completed or are ready to start 
radiotherapy) and patients with relapsing or persistent disease after primary 
surgery and radiotherapy.  All patients must have completed all anticipated 
surgery (biopsy, partial resection, or apparently complete resection), and 
postoperative recovery must be complete.  The newly diagnosed (postoperative 
and ready to start radiotherapy) patients must be registered to the initial 
part of this study, which will assign radiotherapy; these patients must begin 
radiotherapy within 24 hours after registration.  For both newly diagnosed 
patients and those with relapsed or persistent disease, chemotherapy will 
begin no sooner than 4 weeks after completion of radiotherapy in order to 
achieve maximal radiation response prior to randomization (this requirement of 
a 4-week interval between completion of radiotherapy and initiation of 
chemotherapy may be waived in cases of CT-documented progressive tumor growth 
during or immediately after radiotherapy).  There may have been no prior 
cytotoxic chemotherapy, immunomodulatory therapy, or differentiation-inducing 
agent therapy, but prior steroid therapy is allowed and steroids may be 
administered while on protocol for control of cerebral edema.  Prior 
administration of radiation sensitizers and protectors is permitted, but not 
encouraged, and is limited to nitroimidazoles, WR2721, and Flusol.  Patients 
with serious clinical compromise in pulmonary function should not be 
considered for randomization, but patients should not be screened with PFTs 
prior to randomization because this aspect of the study is to identify the 
fraction of patients who might be randomized to receive BCNU but are rejected 
because of inadequate PFT parameters.  Baseline PFTs with spirometry and CO 
diffusion capacity corrected for alveolar volume and hemoglobin should be 
determined on patients randomized to receive BCNU before any BCNU is 
administered, and the corrected diffusion capacity must be at least 60% of the 
predicted value.  Patients randomized to the BCNU arm who have a corrected 
diffusion capacity of less than 60% receive AZQ as on the AZQ arm and receive 
follow-up PFT evaluation.  The SWOG performance status must be 2 or better 
(Karnosky 60% or better), and patients must have a life expectancy of greater 
than 6 weeks.  The general medical condition must be such that patients can 
tolerate the marked myelosuppression that may develop during protocol 
treatment.  Any coexistent serious medical problem, such as recent myocardial 
infarction, current requirement for anticoagulant therapy, bleeding gastric 
ulcer, unstable diabetes mellitus, or serious compromise of pulmonary 
function, excludes, as does the presence of an active infection or a known 
history of severe allergic reaction to iodine-based radiocontrast agents.  The 
following minimum laboratory parameters of organ function must have been 
determined within 14 days of randomization:  platelets at least 125,000; 
hemoglobin at least 9.5 g/dl; hematocrit at least 30%; absolute granulocytes 
at least 1,500; serum creatinine less than 2.0 mg/dl; serum transaminases and 
bilirubin less than twice normal; and normal PT and PTT.  There may be no 
history of a second malignancy other than adequately treated in situ cervical 
carcinoma and nonmelanomatous skin cancer.  Pregnant and lactating women are 
excluded, and those of childbearing potential must have a negative serum 
beta-HCG.

Expected Enrollment

200 patients will be entered in about 40 months.  An interim analysis is 
planned after 150 patients have been entered (about 24 months) to evaluate 
whether early termination is indicated.

Outline

Randomized study.
Arm I:  Single-agent Chemotherapy.  Diaziquone, Aziridinylbenzoquinone, AZQ, 
NSC-182986.
Arm II:  Single-agent Chemotherapy.  Carmustine, BCNU, NSC-409962.

Jaeckle KA, Eyre HJ, Townsend JJ, et al.: Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 16 (10): 3310-5, 1998.[PUBMED Abstract]

Jaeckle KA, Upchurch C, Green SJ, et al.: Phase III randomized trial of infusional AZQ (diaziquone) versus IV BCNU for supratentorial malignant astrocytoma (MA): SWOG 8737. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-496, 177, 1994.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Harmon Eyre, MD, Protocol chair		Ph: 801-585-0303; 877-585-0303