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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: octreotide acetate; Drug: tamoxifen citrate

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.

• Study Type: Interventional
• Enrollment (Actual): 667
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • British Columbia Cancer Agency - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency
    • Victoria, British Columbia, Canada, V8R 1J8
      • British Columbia Cancer Agency - Vancouver Island Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital, Barrie
    • Hamilton, Ontario, Canada, L8V 5C2
      • Cancer Care Ontario-Hamilton Regional Cancer Centre
    • Kingston, Ontario, Canada, K7L 5P9
      • Kingston Regional Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • Cancer Care Ontario-London Regional Cancer Centre
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Centre
    • Mississauga, Ontario, Canada, L5M 2N1
      • Credit Valley Hospital
    • North York, Ontario, Canada, M2E 1K1
      • North York General Hospital, Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1Y 4K7
      • Ottawa Regional Cancer Centre - Civic Campus
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Regional Cancer Center - General Division
    • Sault Sainte Marie, Ontario, Canada, P6B 1Y5
      • Algoma District Medical Group
    • St. Catharines, Ontario, Canada, L2R 5K3
      • Hotel Dieu Hospital - St. Catharines
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre, Sudbury
    • Thunder Bay, Ontario, Canada, P7A 7T1
      • Northwestern Ontario Regional Cancer Centre, Thunder Bay
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5S 1B6
      • Women's College Campus, Sunnybrook and Women's College Health Science Center
    • Toronto, Ontario, Canada, M6R 1B5
      • Saint Joseph's Health Centre - Toronto
    • Weston, Ontario, Canada, M9N 1N8
      • Humber River Regional Hospital
    • Windsor, Ontario, Canada, N8W 2X3
      • Cancer Care Ontario - Windsor Regional Cancer Centre
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
      • Queen Elizabeth Hospital, PEI
  • Quebec
    • Fleurimont, Quebec, Canada, J1H 5N4
      • Centre Universitaire de Sante de l'Estrie - Site Fleurimont
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite' de Montreal
    • Montreal, Quebec, Canada, H2W 1T8
      • Hotel Dieu de Montreal
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
    • Montreal, Quebec, Canada, H2L-4M1
      • Centre Hospitalier de l'Université de Montréal
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrament, Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • L'Hopital Laval
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's/Duluth Clinic Health System
    • Duluth, Minnesota, United States, 55805
      • Duluth Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 116 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Octreotide	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)
Active Comparator: Tamoxifen	Drug: tamoxifen citrate; 20 mg PO for 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival	6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	6 years
Recurrence-free survival	6 years
Insulin-like growth factor measures	6 years
Quality of Life	6 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Michael N. Pollak, MD, Jewish General Hospital

Publications and helpful links

General Publications

• 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 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): A-524, 2006.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 1996
• Primary Completion (Actual): December 7, 2007
• Study Completion (Actual): April 23, 2010

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: June 15, 2004
• First Posted (Estimate): June 16, 2004

Study Record Updates

• Last Update Posted (Actual): April 1, 2020
• Last Update Submitted That Met QC Criteria: March 30, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer; stage III breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen; Octreotide
• Other Study ID Numbers: MA14; CAN-NCIC-MA14; NCI-V96-1060; CDR0000065135 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No