Octreotide, Tamoxifen, and Chemotherapy in Treating Women With Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: cyclophosphamide (Drug); doxorubicin hydrochloride (Drug); octreotide pamoate (Drug); tamoxifen citrate (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Surgical Adjuvant Breast and Bowel Project (NSABP)

Official(s) and/or principal investigator(s):
Richard G. Margolese, MD, Study Chair, Affiliation: Jewish General Hospital

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to study the effectiveness of tamoxifen, octreotide, and chemotherapy in treating women who have stage I or stage II breast cancer.

Official title: A Clinical Trial to Evaluate the Benefit of Adding Octreotide (SMS 201-995 PA LAR) to Tamoxifen Alone or to Tamoxifen and Chemotherapy in Patients With Axillary Node-Negative, Estrogen-Receptor-Positive, Primary Invasive Breast Cancer

Study design: Treatment

Detailed description: OBJECTIVES: I. Determine whether the addition of octreotide pamoate to tamoxifen alone or to tamoxifen and chemotherapy improves the disease free survival of patients with primary invasive breast cancer with estrogen receptor (ER) positive tumors and histologically negative axillary lymph nodes or histologically negative sentinel lymph nodes if participating in NSABP B-32. II. Determine whether the rate of endometrial cancer associated with tamoxifen is altered by the concurrent administration of octreotide pamoate. III. Determine whether the addition of octreotide pamoate to tamoxifen decreases the rate of opposite breast cancer more than tamoxifen alone. IV. Evaluate the incidence of gallstone formation (including the development of symptoms and complications of biliary tract disease), hyper and hypoglycemia, hypothyroidism, and vitamin B12 deficiency in patients treated with octreotide pamoate in comparison with patients not treated with octreotide pamoate.

OUTLINE: This is a randomized study. Patients are randomized into one of four treatment arms. Arm I: Patients receive oral tamoxifen (TMX) daily continously for 5 years. Lumpectomy patients receive breast radiotherapy following recovery from surgery. Arm II: Patients receive TMX as in Arm I and octreotide pamoate (SMS 201-995 pa LAR) intramuscularly (IM) every 21 days for 4 doses, followed by octreotide pamoate IM for 28 days for 23 additional doses. Lumpectomy patients receive breast radiotherapy following recovery from surgery. Arm III: Patients receive doxorubicin (DOX) IV and cyclophosphamide (CTX) IV every 3 weeks for 4 courses and TMX as in Arm I. Lumpectomy patients receive breast radiotherapy after recovery from chemotherapy. Arm IV: Patients receive DOX and CTX as in Arm III, TMX as in Arm I, and octreotide pamoate as in Arm II. Patients receive TMX and octreotide pamoate on day 1 of first course of chemotherapy. Lumpectomy patients receive breast radiotherapy after recovery from chemotherapy.

PROJECTED ACCRUAL: Total accrual of 3,000 patients will be acrrued for this study over 5 years.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS: Histologically confirmed Stage I, IIA or IIB invasive adenocarcinoma of the breast with T1-3, pN0 and M0 classification Must have undergone total mastectomy or lumpectomy followed by an axillary dissection or sentinel node resection if participating in NSABP B-32 Histologically negative axillary lymph nodes OR Histologically negative sentinel lymph nodes if participating in NSABP B-32 Lumpectomy and axillary dissection acceptable only if margins of resected specimen are histologically free of invasive tumor or ductal carcinoma in situ and other dominant masses within the ipsilateral breast remnant are histologically confirmed to be benign Additional operation after resection is allowed in order to obtain clear margins No bilateral malignancy of the breast ER positive tumors as defined by at least one of the following: At least 10 fmol/mg cytosol protein by either dextran-coated charcoal or sucrose density gradient methods Positive or not definitely negative results by the enzyme immunoassay method (EIA) or by immunocytochemical assay No more than 63 days from time of initial cytologic or histologic diagnosis of breast cancer till randomization No bone metastases (confirmation must be made for those with skeletal pain) Tumor must be no greater than 5 cm in its greatest dimension for patients who are treated by lumpectomy and axillary dissection Hormone receptor status: Estrogen receptor positive

PATIENT CHARACTERISTICS: Age: Not specified Sex: Female Menopausal status: Not specified Life expectancy: At least 10 years (excluding diagnosis of cancer) Performance status: Not specified Hematopoietic: WBC at least 4,000/mm3 Platelet count postoperative at least 100,000/mm3 Hepatic: Bilirubin normal SGOT/SGPT normal Renal: Creatinine normal Cardiovascular: No cardiac disease that would preclude the use of doxorubicin (for patients who are to receive adjuvant chemotherapy in this study), including: Myocardial infarction Angina pectoris that requires antianginal medication History of congestive heart failure Arrhythmia associated with concurrent heart failure or cardiac dysfunction Valvular disease with cardiac compromise Cardiomegaly or ventricular hypertrophy unless left ventricular function is within normal limits Poorly controlled hypertension Other: No prior invasive breast cancer or ductal carcimoma in situ No systemic disease that would preclude patients from any part of study No history of symptomatic gallbladder or biliary tract disease unless patient has undergone cholecystectomy No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude No prior nonbreast malignancies in past 10 years except: Squamous or basal cell carcinoma of the skin that has been effectively treated Carcinoma in situ of the cervix that has been treated by operation only Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by segmented resection only No psychiatric or addictive disorders Not pregnant or nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for breast cancer Chemotherapy: No prior chemotherapy for breast cancer No prior anthracycline therapy for patients who are to receive adjuvant chemotherapy in this study Endocrine therapy: No prior endocrine therapy for breast cancer Must discontinue any sex hormonal therapy before prior to and during study Radiotherapy: No prior radiotherapy for breast cancer No breast radiation therapy before randomization for patients who receive lumpectomy Surgery: See Disease Characteristics At least 2 weeks since last surgical procedure Other: No concurrent cyclosporine therapy No concurrent heparin or warfarin anticoagulation therapy

Baptist Medical Center - Birmingham, Birmingham, Alabama 35213, United States

Huntsville Hospital System, Huntsville, Alabama 35801, United States

MBCCOP - University of South Alabama, Mobile, Alabama 36688, United States

CCOP - Greater Phoenix, Phoenix, Arizona 85006-2726, United States

CCOP - Bay Area Tumor Institute, Oakland, California 94609-3305, United States

CCOP - Santa Rosa Memorial Hospital, Santa Rosa, California 95403, United States

Kaiser Permanente Medical Center - Vallejo, Vallejo, California 94589, United States

Loma Linda University Medical Center, Loma Linda, California 92354, United States

Scripps Clinic and Research Foundation - La Jolla, La Jolla, California 92037, United States

Sutter Cancer Center, Sacramento, California 95816, United States

University of California San Diego Cancer Center, La Jolla, California 92093-0658, United States

CCOP - Colorado Cancer Research Program, Inc., Denver, Colorado 80209-5031, United States

Hartford Hospital, Hartford, Connecticut 06102-5037, United States

CCOP - Christiana Care Health Services, Wilmington, Delaware 19899, United States

Baptist Regional Cancer Institute - Jacksonville, Jacksonville, Florida 32207, United States

CCOP - Mount Sinai Medical Center, Miami Beach, Florida 33140, United States

MD Anderson Cancer Center Orlando, Orlando, Florida 32806, United States

Ocala Oncology Center, Ocala, Florida 34474, United States

Sarasota Memorial Hospital, Sarasota, Florida 34239, United States

CCOP - Atlanta Regional, Atlanta, Georgia 30342-1701, United States

Winship Cancer Center, Atlanta, Georgia 30322, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States

CCOP - Central Illinois, Springfield, Illinois 62526, United States

Highland Park Hospital, Highland Park, Illinois 60035-2497, United States

Illinois Masonic Medical Center, Chicago, Illinois 60657, United States

Rockford Clinic, Rockford, Illinois 61103, United States

Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, United States

West Suburban Hospital Medical Center, Oak Park, Illinois 60302, United States

Community Hospitals of Indianapolis - Regional Cancer Center, Indianapolis, Indiana 46219, United States

Memorial Hospital of South Bend, South Bend, Indiana 46601, United States

Methodist Cancer Center - Indianapolis, Indianapolis, Indiana 46206-1367, United States

CCOP - Cedar Rapids Oncology Project, Cedar Rapids, Iowa 52403-1206, United States

CCOP - Iowa Oncology Research Association, Des Moines, Iowa 10309-1016, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536-0093, United States

Norton Healthcare System, Louisville, Kentucky 40202-5070, United States

CCOP - Ochsner, New Orleans, Louisiana 70121, United States

Louisiana State University Medical Center - New Orleans, New Orleans, Louisiana 70112, United States

Eastern Maine Medical Center, Bangor, Maine 04401, United States

Franklin Square Hospital Center, Baltimore, Maryland 21237, United States

Berkshire Medical Center, Pittsfield, Massachusetts 01201, United States

Boston Medical Center, Boston, Massachusetts 02118, United States

Lahey Clinic - Burlington, Burlington, Massachusetts 01805, United States

New England Medical Center Hospital, Boston, Massachusetts 02111, United States

CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids, Michigan 49503, United States

CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States

Michigan State University, East Lansing, Michigan 48824, United States

CCOP - Duluth, Duluth, Minnesota 55805, United States

Keesler Medical Center - Keesler AFB, Keesler AFB, Mississippi 39534-2576, United States

CCOP - Kansas City, Kansas City, Missouri 64131, United States

CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States

St. Louis University School of Medicine, Saint Louis, Missouri 63104, United States

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States

CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68131, United States

Methodist Cancer Center - Omaha, Omaha, Nebraska 68114, United States

CCOP - Southern Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States

CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States

Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States

Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States

University of New Mexico Cancer Research & Treatment Center, Albuquerque, New Mexico 87131, United States

Albany Regional Cancer Center, Albany, New York 12208, United States

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse, New York 13210, United States

Genesee Hospital - Rochester, Rochester, New York 14607, United States

Mount Sinai Medical Center, NY, New York, New York 10029, United States

Staten Island University Hospital, Staten Island, New York 10305, United States

CCOP - Southeast Cancer Control Consortium, Winston-Salem, North Carolina 27104-4241, United States

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157-1082, United States

East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, United States

Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States

Akron City Hospital, Akron, Ohio 44309, United States

Arthur G. James Cancer Hospital - Ohio State University, Columbus, Ohio 43210, United States

Barrett Cancer Center, The University Hospital, Cincinnati, Ohio 45219, United States

CCOP - Columbus, Columbus, Ohio 43206, United States

CCOP - Dayton, Kettering, Ohio 45429, United States

CCOP - Toledo Community Hospital Oncology Program, Toledo, Ohio 43623-3456, United States

Good Samaritan Hospital - Cincinnati, Cincinnati, Ohio 45220, United States

Jewish Hospital of Cincinnati, Inc., Cincinnati, Ohio 45236, United States

Meridia South Pointe Hospital, Cleveland, Ohio 44122, United States

Mount Sinai Medical Center - Cleveland, Cleveland, Ohio 44122, United States

CCOP - St. Francis Hospital/Natalie Warren Bryant Cancer Center, Tulsa, Oklahoma 74136, United States

CCOP - Columbia River Program, Portland, Oregon 97213, United States

Oregon Cancer Center at Oregon Health Sciences University, Portland, Oregon 97201-3098, United States

Albert Einstein Cancer Center, Philadelphia, Pennsylvania 19141, United States

CCOP - MainLine Health, Wynnewood, Pennsylvania 19096, United States

Reading Hospital and Medical Center, Reading, Pennsylvania 19612-6052, United States

St. Luke's Network - Bethlehem, Bethlehem, Pennsylvania 18015, United States

University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, United States

York Hospital, York, Pennsylvania 17315, United States

Jewish General Hospital - Montreal, Montreal, Quebec H3T 1E2, Canada

Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada

Kent County Memorial Hospital - Rhode Island, Warwick, Rhode Island 02886, United States

Rhode Island Hospital, Providence, Rhode Island 02903, United States

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States

CCOP - Sioux Community Cancer Consortium, Sioux Falls, South Dakota 57105-1080, United States

University of Texas Health Center at Tyler, Tyler, Texas 75710, United States

Utah Valley Regional Medical Center - Provo, Provo, Utah 84604, United States

Eastern Virginia Medical School, Norfolk, Virginia 23507, United States

Massey Cancer Center, Richmond, Virginia 23298-0037, United States

MBCCOP - Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Oncology and Hematology Associates of Southwest Virginia, Inc., Roanoke, Virginia 24014, United States

Virginia Oncology Associates, Newport News, Virginia 23606, United States

CCOP - Northwest, Tacoma, Washington 98405-0986, United States

CCOP - Virginia Mason Research Center, Seattle, Washington 98101, United States

Puget Sound Oncology Consortium, Seattle, Washington 98109, United States

Camden-Clark Memorial Hospital, Parkersburg, West Virginia 26102, United States

CCOP - Marshfield Medical Research and Education Foundation, Marshfield, Wisconsin 54449, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

Soran A, Nesbitt L, Mamounas EP, Lembersky B, Bryant J, Anderson S, Brown A, Passarello M. Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials. 2006;3(5):478-85.

Starting date: May 1997
Last updated: May 23, 2008