Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	Not specified	NCI	NSABP-B-29 NCT00002967

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.

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

Expected Enrollment

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

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.

Soran A, Nesbitt L, Mamounas EP, et al.: Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials 3 (5): 478-85, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Richard Margolese, MD, Protocol chair		Ph: 514-342-3504

Registry Information
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
Trial Start Date		1997-05-01
Registered in ClinicalTrials.gov		NCT00002967
Date Submitted to PDQ		1997-05-01
Information Last Verified		2006-11-09
NCI Grant/Contract Number		U10-CA12027