Tamoxifen With or Without Octreotide in Treating Postmenopausal Women With Stage I, Stage II, or Stage III Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Randomized Trial of Antiestrogen Therapy Versus Combined Antiestrogen and Octreotide Therapy in the Adjuvant Treatment of Breast Cancer in Post-Menopausal Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002864
• Other study ID #: MA14
• Secondary ID: CAN-NCIC-MA14NCI
• Status: Completed
• Phase: Phase 3
• Start date: September 24, 1996
• Est. completion date: April 23, 2010

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen with or without octreotide may fight breast cancer by blocking the uptake of estrogen. It is not yet known which treatment regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with or without octreotide in treating postmenopausal women who have stage I, stage II, or stage III breast cancer.

Description:

OBJECTIVES: I. Compare event-free, recurrence-free, and overall survival following adjuvant therapy with tamoxifen alone vs. tamoxifen plus octreotide long-acting release formulation in postmenopausal women with stage I/II/III breast cancer. II. Compare the toxicity and quality of life associated with each treatment regimen. III. Compare the effects of each treatment regimen on insulin-like growth factor-I (IGF-I) physiology, and study the relationship between IGF-I physiology and outcome.

OUTLINE: This is a randomized study. Patients are stratified by participating institution, when and whether they receive adjuvant chemotherapy, axillary lymph node status, and hormone receptor status. All patients are randomized within 12 weeks of definitive surgery. Patients receiving adjuvant chemotherapy prior to protocol treatment are randomized within 6 weeks after the last dose of chemotherapy. One group of patients receives daily oral tamoxifen, while a second group receives daily oral tamoxifen plus octreotide (long-acting release formulation) by monthly depot injection. Treatment in both groups continues for 5 years or until disease recurrence or development of a second malignancy. Patients are followed monthly for 4 months, every 4 months for 3 years, and every 6 months thereafter.

PROJECTED ACCRUAL: A total of 850 patients will be entered over 4.2 years in this multicenter study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 667
• Est. completion date: April 23, 2010
• Est. primary completion date: December 7, 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 120 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast that is potentially curable Prior treatment with one of the following therapies required: Segmental mastectomy (lumpectomy) followed by radiotherapy Chest wall irradiation allowed only in patients with T4 dermal involvement on pathologic diagnosis Further excision or boost radiotherapy to the tumor bed recommended if microscopic disease found at mastectomy margins Total mastectomy Chest wall irradiation required if microscopic disease found at mastectomy margins Clinical stage T1-3a N0-2 M0 disease prior to surgery The following T4 features exclude: Chest wall extension Edema (including peau d'orange) Skin ulceration Satellite skin nodules confined to same breast Inflammatory carcinoma Pathologic stage T1-4 NX-2 M0 disease following surgery Eligible T4 tumors are those with dermal involvement on pathology assessment only Pathologic assessment of axillary lymph nodes required May be omitted in patients with clinical N0 status provided other entry criteria are met No bilateral breast cancer without complete resection of both sides Hormone receptor status: Estrogen and progesterone receptor status determined from primary tumor when possible by quantitative biochemical methods or immunohistochemistry Results recorded as positive or negative if immunohistochemistry used Unknown status does not exclude provided other entry criteria are met

PATIENT CHARACTERISTICS: Age: Postmenopausal Sex: Women only Menopausal status:

Postmenopausal by one or more of the following: Amenorrhea lasting more than 1 year in women under 50 years of age with no prior hysterectomy No menses for 6 months prior to breast surgery in women 50 years of age and over with no prior hysterectomy Documented oophorectomy prior to breast cancer diagnosis Luteinizing hormone and follicle-stimulating hormone values diagnostic of postmenopausal status by local laboratory criteria Women 50 years of age and over with prior hysterectomy Performance status: ECOG 0-2 Life expectancy: At least 5 years Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: (unless metastatic disease ruled out by radiologic exam) AST or ALT less than twice normal Alkaline phosphatase less than twice normal Renal: Not specified Other: No symptomatic gallbladder disease or cholecystitis No intercurrent illness that reduces life expectancy to less than 5 years No other major medical or psychiatric illness that precludes study treatment or follow-up No second malignancy within 5 years except: Adequately treated basal cell skin carcinoma Adequately treated cancer of the cervix, endometrium, colon, or thyroid Able and willing to complete quality-of-life questionnaires in English or French Illiteracy, loss of sight, or other inability to complete questionnaires does not exclude Accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: Prior or concurrent adjuvant chemotherapy allowed at investigator's discretion Recommended regimens: CMF (cyclophosphamide/methotrexate/fluorouracil) CEF (cyclophosphamide/etoposide/fluorouracil) AC (doxorubicin/cyclophosphamide) Choice of adjuvant chemotherapy regimen defined prior to randomization if given concurrently with protocol therapy Endocrine therapy: No estrogen, progestins, or androgen therapy for a period of more than 30 days following pathologic diagnosis of breast cancer Prior tamoxifen allowed All hormonal therapy discontinued prior to randomization Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• octreotide acetate
Octreotide LAR (SMS 201-995 pa LAR) 90 mg depot injection monthly for 2 years (plus Tamoxifen 20 mg PO daily for 5 years)
• tamoxifen citrate
20 mg PO for 5 years

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital, Barrie	Barrie	Ontario
Canada	Queen Elizabeth Hospital, PEI	Charlottetown	Prince Edward Island
Canada	Centre Universitaire de Sante de l'Estrie - Site Fleurimont	Fleurimont	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Centre Hospitalier de l'Universite' de Montreal	Montreal	Quebec
Canada	Hotel Dieu de Montreal	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	North York General Hospital, Ontario	North York	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Regional Cancer Center - General Division	Ottawa	Ontario
Canada	Ottawa Regional Cancer Centre - Civic Campus	Ottawa	Ontario
Canada	Hopital du Saint-Sacrament, Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Algoma District Medical Group	Sault Sainte Marie	Ontario
Canada	Hotel Dieu Hospital - St. Catharines	St. Catharines	Ontario
Canada	L'Hopital Laval	Ste-Foy	Quebec
Canada	Northeastern Ontario Regional Cancer Centre, Sudbury	Sudbury	Ontario
Canada	British Columbia Cancer Agency - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Northwestern Ontario Regional Cancer Centre, Thunder Bay	Thunder Bay	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Saint Joseph's Health Centre - Toronto	Toronto	Ontario
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	Women's College Campus, Sunnybrook and Women's College Health Science Center	Toronto	Ontario
Canada	BC Cancer Agency	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Humber River Regional Hospital	Weston	Ontario
Canada	Cancer Care Ontario - Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Duluth Clinic	Duluth	Minnesota
United States	St. Mary's/Duluth Clinic Health System	Duluth	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Ali SM, Chapman JW, Demers L, et al.: Effect of adjuvant chemotherapy on bone resorption marker beta C-telopeptide (B-CTX) in postmenopausal women. [Abstract] J Clin Oncol 27 (Suppl 15): A-594, 2009.

Piura E, Chapman JW, Lipton A, et al.: Serum 1-OH vitamin D (D) and prognosis of postmenopausal breast cancer (BC) patients: NCIC-CTG MA14 trial. [Abstract] J Clin Oncol 27 (Suppl 15): A-534, 2009.

Pollak M, Pritchard K, Whelan T, et al.: The NCIC CTG MA.14 experience with the gallbladder toxicity of octreotide pamoate (oncolar) in a postmenopausal patient population undergoing adjuvant treatment for stage 1-3 breast cancer. Eur J Cancer 38(suppl 3)

Pollak MN, Chapman JW, Pritchard KI, et al.: NCIC-CTG MA14 trial: tamoxifen (tam) vs. tam + octreotide (oct) for adjuvant treatment of stage I or II postmenopausal breast cancer. [Abstract] J Clin Oncol 26 (Suppl 15): A-532, 2008.

Pollak MN, Chapman JW, Shepherd L, et al.: Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial. [Abstract] J Clin Oncol 24 (Suppl 18

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		6 years
Secondary	Recurrence-free survival		6 years
Secondary	Overall survival		6 years
Secondary	Insulin-like growth factor measures		6 years
Secondary	Quality of Life		6 years