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	Closed	over 16	NCI	CLB-8741 CALGB-8741

Objectives

I.  Evaluate, in a randomized Phase III trial, the dose-response relationship 
for megestrol acetate in patients with Stage IV ER-positive, PgR-positive, or 
ER-unknown breast carcinoma by comparing results of administration of the 
standard dose vs. 5 times the standard dose vs. 10 times the standard dose.
II.  Determine and compare response frequency, time to progression, time to 
chemotherapy, time to visceral disease, and survival of these patients at the 
three megestrol acetate doses.
III.  Determine the optimal dose of megestrol acetate in these patients 
relative to response and toxicity.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over the age of 16 years 
with histologically documented breast carcinoma known to be Stage IV provided 
that either the primary tumor or a metastasis has been demonstrated to be 
either positive for ER or PgR (at least 7 fmoles/ng of protein) or of unknown 
hormone receptor status.  Patients with a history of bilateral breast cancer, 
either synchronous or metachronous, are eligible if both tumors meet the 
specified receptor criteria.  Patients must have either measurable (i.e., at 
least one tumor mass measurable in 2 perpendicular diameters by either 
physical examination, x-ray, or scan) or evaluable disease.  Evaluable disease 
includes the following:  a frank metastatic pattern on bone scan (all 
suspicious areas must be x-rayed) with elevated alkaline phosphatase; mixed 
lytic and blastic lesions on x-ray; pleural effusions; ascites; and clear 
evidence of disease, e.g., a mass seen only on chest x-ray adjacent to a 
pulmonary infiltrate but not bidimensionally measurable or bone disease 
present on bone scan only.  Patients with nonmeasurable evaluable disease will 
be analyzed separately.  There must have been full recovery from the side 
effects and toxicity related to previous treatment.  There may have been no 
prior treatment with progestational agents for cancer and no recent or current 
use of progestational agents (e.g., for control of menopausal symptoms).  
Except for progestational agents, patients may have received one and only one 
prior hormonal therapy (drugs or surgical manipulation); patients may have 
received the same hormonal therapy on two separate occasions (e.g., tamoxifen 
as adjuvant therapy and as treatment for metastatic disease).  Patients who 
responded to initial hormone therapy must wait 6 weeks before starting 
protocol therapy, while nonresponders (stable disease or progression) may 
enter within 2 weeks of completing prior hormone therapy.  Premenopausal women 
whose initial therapy was bilateral oophorectomy may begin protocol therapy as 
soon as disease progression is obvious.  Patients who develop progressive 
disease while on adjuvant tamoxifen must wait 6 weeks before starting on 
megestrol acetate; the waiting period may be shortened to 2 weeks if there is 
rapidly progressive disease off tamoxifen.  If the adjuvant hormonal therapy 
was discontinued more than 6 weeks prior to development of progressive 
disease, megestrol acetate may be started without delay.  There may have been 
no prior chemotherapy for metastatic disease, although prior adjuvant 
chemotherapy is allowable provided a disease-free period of at least 1 year 
off therapy has intervened.  There may be no current or previous CNS 
metastases, and patients must not have quiescent disease (i.e., no evidence of 
stable disease for 6 months off treatment).  Patients must not have rapidly 
advancing life-threatening visceral disease, e.g., extensive liver metastasis, 
lymphangitic pulmonary spread, or disseminated bone marrow involvement.  
Patients with inflammatory breast cancer are not eligible.  Patients must have 
no known intolerance to progestational agents.  The performance status must be 
0-3, and there must be laboratory evidence of adequate hematologic, renal, and 
hepatic function.  There may have been no second malignancy other than 
curatively treated carcinoma in situ of the cervix or basal cell carcinoma of 
the skin.  There may be no other serious medical illness that would otherwise 
limit survival to less than 2 years.  Patients must be free from uncontrolled 
or serious cardiovascular disease, i.e., myocardial infarction within 6 
months, congestive heart failure, severe or uncontrolled hypertension 
(systolic no greater than 150 and diastolic no greater than 100 mm Hg), and 
there may be no thrombophlebitis, thrombotic disorders, or stroke currently or 
in the past.  Uncontrolled diabetes mellitus also excludes study entry.  Any 
bacterial, viral, or fungal infection or an active duodenal ulcer must be 
brought under control before entry.  Pregnancy excludes.  Patients must be 
concurrently enrolled on protocol CLB-8864 (Assessing Quality of Life During a 
Dose-Response Trial of Megestrol Acetate in Advanced Breast Cancer Patients); 
protocols CLB-8662 and CLB-8862 are optional companion studies.

Expected Enrollment

A total of 373 patients (118 evaluable patients per arm) will be enrolled.  As 
of 06/90, 326 patients had been registered, and it was anticipated that 
accrual goals would be reached by 11/90.

Outline

Randomized study.
Arm I:  Single-agent Progestin Treatment.  Megestrol acetate, MA, MEG, 
NSC-71423.  Standard dose.
Arm II:  Single-agent Progestin Treatment.  MEG.  5 times standard dose.
Arm III:  Single-agent Progestin Treatment.  MEG.  10 times standard dose.

Abrams J, Aisner J, Cirrincione C, et al.: Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741. J Clin Oncol 17 (1): 64-73, 1999.[PUBMED Abstract]

Kornblith AB, Hollis DR, Zuckerman E, et al.: Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B. J Clin Oncol 11 (11): 2081-9, 1993.[PUBMED Abstract]

Abrams JS, Cirrincione C, Aisner J, et al.: A phase III dose response trial of megestrol acetate (MA) in metastatic breast cancer (MBC). [Abstract] Proceedings of the American Society of Clinical Oncology 11: A-50, 56, 1992.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Joseph Aisner, MD, Protocol chair		Ph: 732-235-7401 Email: aisnerjo@umdnj.edu