Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Hormone Therapy in Treating Postmenopausal Women With Receptor-Positive Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	postmenopausal	NCI	E-EB193 CLB-9443, NCCTG-953052, SWOG-9514, INT-0151, NCT00002646

Objectives

I.  Compare disease free survival and overall survival of postmenopausal women 
with stage II or IIIA breast cancer treated with tamoxifen (TMX) and 
fenretinide (HPR) vs TMX and placebo.

II.  Gain wider experience in the use and toxicity of combined TMX/HPR in 
these patients.

III.  Obtain tumor tissue samples, as feasible, from these patients for future 
biologic studies.

Entry Criteria

Disease Characteristics:

Histologically confirmed adenocarcinoma of the breast

Pathologic stage T1-3, N1-2, M0
  No clinical or pathologic T4 disease
     No primary tumor fixed to chest wall
     No axillary nodes fixed to chest wall or neurovascular bundle
     No preoperative arm edema
     No clinical skin involvement (microscopic focal dermal invasion or dermal
        lymphatic involvement eligible)
  No clinical N2 disease

Modified radical mastectomy or lumpectomy required prior to entry
  Sentinel node biopsy allowed
  Randomization required within 12 weeks from definitive surgery
     Surgery dated from mastectomy or axillary dissection for lumpectomy
  No positive deep mastectomy margins

Radiotherapy planned within 12 weeks following axillary node dissection for
lumpectomy patients

Synchronous bilateral breast cancer eligible
  If tumor is at least 2 cm, then nodes not involved
  If no tumor is at least 2 cm, then at least 1 node must be involved
  Both invasive primaries receptor-positive

Previously treated, noninvasive breast cancer eligible

No prior invasive breast cancer

No adenoid cystic, squamous, or sarcomatous histology

Hormone receptor status:
  Estrogen- or progesterone-receptor positive, i.e.:
     At least 10 fmole/mg cytosol protein by ligand-binding assay OR
     Receptor positive by immunocytochemistry

Prior/Concurrent Therapy:

No prior chemotherapy or hormonal therapy for breast cancer except:
  Up to 1 month of tamoxifen if started by a non participating physician
  At least 2 weeks since hormone replacement therapy
  No concurrent megestrol

Patient Characteristics:

Age:
  65 and over OR
  Postmenopausal and ineligible/inappropriate for or declined other active
   node positive adjuvant studies

Sex:
  Female

Menopausal status:
  Postmenopausal, defined as:
     At least 1 year since last menstrual period
     Hysterectomized with bilateral oophorectomy
     Hysterectomized with 1 or both ovaries remaining and either:
        Over 60
        FSH in postmenopausal range
     Not surgically castrated, under 60, and on HRT
        FSH elevated 2 weeks after HRT discontinued

Performance status:
  Not specified

Life expectancy:
  At least 7 years except for breast cancer

Hematopoietic:
  WBC greater than 3,000/mm3
  Platelet count at least 100,000/mm3
  Hemoglobin at least 10 g/dL

Hepatic:
  Bilirubin no greater than 1.5 mg/dL
  AST less than 2 times normal

Renal:
  Creatinine no greater than 2.0 mg/dL
  BUN no greater than 25.0 mg/dL

Other:
  No extensive macular degeneration on exam within 1 year of entry, e.g.:
     No exudative or atrophic macular lesions that reduce corrected vision to
     less than 20/40
  Health adequate for protocol treatment
  No nutritional supplementation except single daily multivitamin
  No other vitamin A supplements
  Gynecologic exam within the past year required of women who retain a uterus
  No second malignancy within the past 10 years except:
     Inactive nonmelanomatous skin cancer
     Carcinoma in situ of the cervix
     Prior noninvasive contralateral breast cancer

Expected Enrollment

A total of 1,500 patients will be accrued for this study over approximately 3 
years. 

Outline

This is a randomized, double blind, placebo controlled, multicenter study.  
Patients are stratified by participating institution, age (under 70 vs 70 and 
over), node dissection (yes vs no), number of involved nodes (0 vs 1-3 vs 4 or 
more), and number of removed nodes (1-5 vs 6 or more).

All patients receive oral tamoxifen daily for at least 5 years, beginning 
immediately after randomization.

Patients also receive either oral fenretinide or oral placebo daily for 5 
years, beginning within 2 weeks after completion of any radiotherapy, or 
within 2 weeks of randomization, if no radiation.

Patients are followed during and after treatment every 4 months for 2 years, 
every 6 months for 3 years, then annually thereafter. 

Cobleigh MA, Gray R, Graham M, et al.: Fenretinide (FEN) vs placebo in postmenopausal breast cancer patients receiving adjuvant tamoxifen (TAM), an Eastern Cooperative Oncology Group Phase III Intergroup Trial (EB193, INT-0151). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A328, 2000.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Melody Cobleigh, MD, Protocol chair		Ph: 312-942-2242

Southwest Oncology Group

George Budd, MD, Protocol chair		Ph: 216-444-6480; 800-862-7798

Cancer and Leukemia Group B

Mark Graham, MD, Protocol chair(Contact information may not be current)		Ph: 919-966-4431 Email: gman@med.unc.edu

North Central Cancer Treatment Group

James Ingle, MD, Protocol chair		Ph: 507-284-3731 Email: ingle.james@mayo.edu

Registry Information
Official Title		PHASE III DOUBLE-BLIND, PLACEBO-CONTROLLED, PROSPECTIVE RANDOMIZED COMPARISON OF ADJUVANT THERAPY WITH TAMOXIFEN VS. TAMOXIFEN AND FENRETINIDE IN POSTMENOPAUSAL WOMEN WITH INVOLVED AXILLARY LYMPH NODES AND POSITIVE RECEPTORS
Trial Start Date		1995-10-04
Trial Completion Date		2004-02-25
Registered in ClinicalTrials.gov		NCT00002646
Date Submitted to PDQ		1995-10-04
Information Last Verified		2009-03-04
NCI Grant/Contract Number		U10-CA21115, U10-CA31946, U10-CA32102

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