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 women with stage I or stage II breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer invasive ductal breast carcinoma stage II breast cancer	Drug: cyclophosphamide  Drug: doxorubicin  Drug: octreotide pamoate  Drug: tamoxifen	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Criteria

PROTOCOL ENTRY 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

--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

--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

Alabama
      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
Arizona
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
California
      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
Colorado
      CCOP - Colorado Cancer Research Program, Inc., Denver,  Colorado,  80209-5031,  United States
Connecticut
      Hartford Hospital, Hartford,  Connecticut,  06102-5037,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
Florida
      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
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Winship Cancer Center, Atlanta,  Georgia,  30322,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      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
Indiana
      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
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  10309-1016,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Kentucky
      Lucille Parker Markey Cancer Center, University of Kentucky, Lexington,  Kentucky,  40536-0093,  United States
      Norton Healthcare System, Louisville,  Kentucky,  40202-5070,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      Louisiana State University Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
Maine
      Eastern Maine Medical Center, Bangor,  Maine,  04401,  United States
Maryland
      Franklin Square Hospital Center, Baltimore,  Maryland,  21237,  United States
Massachusetts
      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
Michigan
      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
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
Missouri
      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
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
      Methodist Cancer Center - Omaha, Omaha,  Nebraska,  68114,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Jersey
      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
New Mexico
      University of New Mexico Cancer Research & Treatment Center, Albuquerque,  New Mexico,  87131,  United States
New York
      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
North Carolina
      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
Ohio
      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
Oklahoma
      CCOP - St. Francis Hospital/Natalie Warren Bryant Cancer Center, Tulsa,  Oklahoma,  74136,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      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
Rhode Island
      Kent County Memorial Hospital - Rhode Island, Warwick,  Rhode Island,  02886,  United States
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57105-1080,  United States
Texas
      University of Texas Health Center at Tyler, Tyler,  Texas,  75710,  United States
Utah
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States
Virginia
      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
Washington
      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
West Virginia
      Camden-Clark Memorial Hospital, Parkersburg,  West Virginia,  26102,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
Canada, Quebec
      Jewish General Hospital - Montreal, Montreal,  Quebec,  H3T 1E2,  Canada
      Montreal General Hospital, Montreal,  Quebec,  H3G 1A4,  Canada

Study chairs or principal investigators

Richard G. Margolese,  Study Chair,  National Surgical Adjuvant Breast and Bowel Project (NSABP)   

Study ID Numbers:  CDR0000065472; NSABP-B-29
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002967
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08