Clinical trial NCT00002967: Octreotide, Tamoxifen, and Chemotherapy in Treating Women With 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
invasive ductal breast carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-09-03
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Baptist Medical Center - Birmingham
state: Alabama
city: Huntsville
country: United States
facility: Huntsville Hospital System
state: Alabama
city: Mobile
country: United States
facility: MBCCOP - University of South Alabama
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Greater Phoenix
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic and Research Foundation - La Jolla
state: California
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center - Vallejo
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Inc.
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Regional Cancer Institute - Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Rush-Presbyterian-St. Luke's Medical Center
state: Illinois
city: Chicago
country: United States
facility: Illinois Masonic Medical Center
state: Illinois
city: Highland Park
country: United States
facility: Highland Park Hospital
state: Illinois
city: Oak Park
country: United States
facility: West Suburban Hospital Medical Center
state: Illinois
city: Rockford
country: United States
facility: Rockford Clinic
state: Illinois
city: Springfield
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Cancer Center - Indianapolis
state: Indiana
city: Indianapolis
country: United States
facility: Community Hospitals of Indianapolis - Regional Cancer Center
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Lexington
country: United States
facility: Lucille Parker Markey Cancer Center, University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Healthcare System
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Medical Center - New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Franklin Square Hospital Center
state: Maryland
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic - Burlington
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshire Medical Center
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids Clinical Oncology Program
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler AFB
state: Mississippi
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Omaha
country: United States
facility: Methodist Cancer Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research & Treatment Center
state: New Mexico
city: Albany
country: United States
facility: Albany Regional Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Rochester
country: United States
facility: Genesee Hospital - Rochester
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University School of Medicine
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Barrett Cancer Center, The University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Jewish Hospital of Cincinnati, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Meridia South Pointe Hospital
state: Ohio
city: Cleveland
country: United States
facility: Mount Sinai Medical Center - Cleveland
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Kettering
country: United States
facility: CCOP - Dayton
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Tulsa
country: United States
facility: CCOP - St. Francis Hospital/Natalie Warren Bryant Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Center at Oregon Health Sciences University
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Network - Bethlehem
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Warwick
country: United States
facility: Kent County Memorial Hospital - Rhode Island
state: Rhode Island
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Puget Sound Oncology Consortium
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Parkersburg
country: United States
facility: Camden-Clark Memorial Hospital
state: West Virginia
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital - Montreal
state: Quebec
Study officials:
affiliation: Jewish General Hospital
name: Richard G. Margolese, MD
role: STUDY_CHAIR
References:
citation: Chapman JA, Costantino JP, Dong B, et al.: Randomized trials of adjuvant tamoxifen versus tamoxifen and octreotide LAR in early-stage breast cancer: NCIC CTG MA.14 and NSABP B-29. [Abstract] J Clin Oncol 30 (Suppl 15): A-538, 2012.
citation: 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. doi: 10.1177/1740774506070747.
citation: Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. doi: 10.1007/s10549-015-3547-4. Epub 2015 Aug 15.