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

NCT ID: NCT00002864

Last Updated: 2020-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 667 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-09-24
• Study Completion Date: 2010-04-23

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Octreotide

Group Type: ACTIVE_COMPARATOR

octreotide acetate

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

tamoxifen citrate

Intervention Type: DRUG

20 mg PO for 5 years

Interventions

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)

Intervention Type: DRUG

tamoxifen citrate

20 mg PO for 5 years

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael N. Pollak, MD

Role: STUDY_CHAIR

Jewish General Hospital

Locations

Duluth Clinic

Duluth, Minnesota, United States

St. Mary's/Duluth Clinic Health System

Duluth, Minnesota, United States

British Columbia Cancer Agency - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BC Cancer Agency

Vancouver, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada

Royal Victoria Hospital, Barrie

Barrie, Ontario, Canada

Northeastern Ontario Regional Cancer Centre, Sudbury

Greater Sudbury, Ontario, 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

Trillium Health Centre

Mississauga, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, 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

Algoma District Medical Group

Sault Ste. Marie, Ontario, Canada

Hotel Dieu Hospital - St. Catharines

St. Catharines, Ontario, Canada

Northwestern Ontario Regional Cancer Centre, Thunder Bay

Thunder Bay, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

St. Michael's Hospital - Toronto

Toronto, Ontario, Canada

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Women's College Campus, Sunnybrook and Women's College Health Science Center

Toronto, Ontario, Canada

Saint Joseph's Health Centre - Toronto

Toronto, Ontario, Canada

Humber River Regional Hospital

Weston, Ontario, Canada

Cancer Care Ontario - Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Queen Elizabeth Hospital, PEI

Charlottetown, Prince Edward Island, Canada

Centre Universitaire de Sante de l'Estrie - Site Fleurimont

Fleurimont, Quebec, Canada

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

McGill University Department of Oncology

Montreal, Quebec, Canada

Centre Hospitalier de l'Universite' de Montreal

Montreal, Quebec, Canada

Hotel Dieu de Montreal

Montreal, Quebec, Canada

Hopital du Saint-Sacrament, Quebec

Québec, Quebec, Canada

L'Hopital Laval

Ste-Foy, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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): A-524, 2006.

Reference Type: RESULT

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): s2-s179, 2002.

Reference Type: RESULT

Sgroi DC, Chapman JA, Badovinac-Crnjevic T, Zarella E, Binns S, Zhang Y, Schnabel CA, Erlander MG, Pritchard KI, Han L, Shepherd LE, Goss PE, Pollak M. Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study. Breast Cancer Res. 2016 Jan 4;18(1):1. doi: 10.1186/s13058-015-0660-6.

Reference Type: DERIVED

PMID: 26728744 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26276354 (View on PubMed)

Bramwell VH, Tuck AB, Chapman JA, Anborgh PH, Postenka CO, Al-Katib W, Shepherd LE, Han L, Wilson CF, Pritchard KI, Pollak MN, Chambers AF. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res. 2014 Jan 22;16(1):R8. doi: 10.1186/bcr3600.

Reference Type: DERIVED

PMID: 24451146 (View on PubMed)

Other Identifiers

CAN-NCIC-MA14

Identifier Type: -

Identifier Source: secondary_id

NCI-V96-1060

Identifier Type: -

Identifier Source: secondary_id

CDR0000065135

Identifier Type: OTHER

Identifier Source: secondary_id

MA14

Identifier Type: -

Identifier Source: org_study_id