Tamoxifen in Treating Women With High-Risk Breast Cancer

NCT00002542 | Completed Phase 3 DMC

• 4 other identifiers: MA12CAN-NCIC-MA12NCI-V93-0323CDR0000063224
• Study Type: interventional
• Target: 672
• Locations: 1 country
• Sites: 48

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase III trial to study the effectiveness of tamoxifen following surgery and chemotherapy in treating women who have stage I breast cancer at high risk of recurrence or stage II or stage III breast cancer.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Interventions

CMF regimen DRUG

cyclophosphamide DRUG

doxorubicin hydrochloride DRUG

epirubicin hydrochloride DRUG

fluorouracil DRUG

methotrexate DRUG

tamoxifen citrate DRUG

radiation therapy RADIATION

Eligibility Criteria

• Age: Up to 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Adenocarcinoma of the breast with 1 or more histologically proven positive axillary nodes OR Adenocarcinoma of the breast with negative axillary nodes or adverse prognostic factors such that the patient is at high risk for recurrence and node negative lesion is characterized by the following features: Tumor at least 1 cm Poorly differentiated, SBR grade III, or MSBR grade V and/or lymphatic/vascular invasion Pathologic review by experienced breast pathologist recommended if grade is unspecified and lymphatic/vascular invasion is absent Disease considered potentially curable and treated by 1 of the following: Complete surgical removal of the breast plus axillary node dissection Partial surgical removal of the breast plus axillary node dissection, with the intention of giving breast irradiation following completion of an adjuvant chemotherapy regimen Regional nodal or chest wall irradiation not prohibited but strongly discouraged No evidence of residual tumor in the axilla following dissection No microscopic evidence of residual tumor at the resection margins following total mastectomy Further excision highly recommended if there is microscopic residual disease present at partial mastectomy margins If further excision is not undertaken, a radiotherapy boost to the tumor bed is required in addition to breast irradiation given following protocol chemotherapy Disease clinically staged prior to surgery as T1-T3a, N0-2, M0 No clinical T4 disease, i.e.: No extension to the chest wall No edema (including peau d'orange) No skin ulceration No satellite skin nodules confined to the same breast No inflammatory carcinoma Disease pathologically staged following surgery as TNM stage I, II, or III (T0-4; N0-2; M0) T4 allowed only with dermal involvement on pathology assessment No evidence of metastatic disease beyond the homolateral axillary nodes on pre-chemotherapy chest x-ray, bone scan (with radiographs of suspicious areas), and abdominal ultrasound (required only if bilirubin, alkaline phosphatase, or AST/ALT are elevated) Simultaneous bilateral breast carcinoma allowed Complete tumor resection on both breasts required Axillary dissection on both sides must meet criteria as above if both sides are clinically node-positive Axillary dissection on the second side optional if the axilla is clinically negative at the time of surgery and the other side is node-positive Adjuvant chemotherapy must begin within 14 weeks of initial pathologic diagnosis Hormone receptor status: Any receptor level allowed (values must be available if biochemical method used; immunocytochemical assay permitted) PATIENT CHARACTERISTICS: Age: Not specified Sex: Female Menopausal status: Pre- or perimenopausal, i.e., meeting at least 1 of the following criteria: Normal menstruation Amenorrhea for less than 1 year (up to 3 years in patients under age 52) Biochemical evidence of ovarian function Hysterectomy without bilateral oophorectomy in patients under age 56 Premenopausal women no greater than age 50 who were started on replacement hormone therapy before amenorrhea are eligible Performance status: ECOG 0-2 prior to chemotherapy Hematopoietic: WBC at least 3,000/mm3 Polymorphs and bands at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: (unless abdominal ultrasound indicates liver metastasis) Alkaline phosphatase no greater than 2 times normal AST and/or ALT no greater than 2 times normal Renal: Not specified Other: No history of serious underlying medical illness or psychiatric or addictive disorder No second malignancy within 5 years except: Curatively treated nonmelanomatous skin cancer Curatively treated endometrium, colon, or thyroid cancer or carcinoma in situ of the cervix No plan for pregnancy during the 5-year study period Fertile women must use effective contraception (other than oral contraception) Accessible for treatment and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy: Colony-stimulating factors allowed (use must be documented) Chemotherapy: No prior chemotherapy No concurrent other cytotoxic therapy Endocrine therapy: Adjuvant tamoxifen (20 mg po daily) allowed up to 2 weeks before or during adjuvant chemotherapy provided drug is discontinued at randomization No long-term prednisone or other hormones Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (48)

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

The Royal Victoria Hospital

Barrie, L4M 6M2, Canada

Location

William Osler Health Centre, Brampton Memorial

Brampton, L6R 3J7, Canada

Location

Tom Baker Cancer Centre

Calgary, T2N 4N2, Canada

Location

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, C1A 8T5, Canada

Location

Cross Cancer Institute

Edmonton, T6G 1Z2, Canada

Location

Regional Cancer Program of the Hopital Regional

Greater Sudbury, P3E 5J1, Canada

Location

QEII Health Sciences Center

Halifax, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, L8V 5C2, Canada

Location

Centre Hospitalier Regional de Lanaudiere

Joliette, J6E 6J2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, K7L 5P9, Canada

Location

L'Hotel-Dieu de Levis

Lévis, G6V 3Z1, Canada

Location

London Regional Cancer Program

London, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, L5M 2N1, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, H2W 1S6, Canada

Location

CHUM - Hotel Dieu du Montreal

Montreal, H2W 1T8, Canada

Location

CHUM - Pavillon Saint-Luc

Montreal, H3X 3J4, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, L3Y 2P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, L1G 2B9, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, K1H 8L6, Canada

Location

Penticton Regional Hospital

Penticton, V2A 3G6, Canada

Location

Peterborough Regional Health Centre

Peterborough, K9H 7B6, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, G1R 2J6, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, G1S 4L8, Canada

Location

University Institute of Cardiology and

Québec, G1V 4G5, Canada

Location

Allan Blair Cancer Centre

Regina, S4T 7T1, Canada

Location

Atlantic Health Sciences Corporation

Saint John, E2L 4L2, Canada

Location

Saskatoon Cancer Centre

Saskatoon, S7N 4H4, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, P6A 2C4, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, J1H 5N4, Canada

Location

Niagara Health System

St. Catharines, L2R 7C6, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, V3V 1Z2, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, P7B 6V4, Canada

Location

Toronto East General Hospital

Toronto, M4C 3E7, Canada

Location

Odette Cancer Centre

Toronto, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, M5G 1X5, Canada

Location

Univ. Health Network-The Toronto General Hospital

Toronto, M5G 2C4, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, M5G 2M9, Canada

Location

Women's College Hospital

Toronto, M5S 1B2, Canada

Location

St. Joseph's Health Centre

Toronto, M6R 1B5, Canada

Location

Trillium Health Centre - West Toronto

Toronto, M9C 1A5, Canada

Location

Humber River Regional Hospital

Toronto, M9N 1N8, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, V8R 6V5, Canada

Location

Windsor Regional Cancer Centre

Windsor, N8W 2X3, Canada

Location

CancerCare Manitoba

Winnipeg, R3E 0V9, Canada

Location

Related Publications (2)

• Bramwell VHC, Pritchard KI, Tu D, et al.: How compliant are patients with oral hormonal therapies? Data from a randomized, placebo controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (NCIC CTG MA.12). [Abstract] Breast Cancer Res Treat 106 (1): A-3055, 2007.

  RESULT

• Bramwell VH, Pritchard KI, Tu D, et al.: Tamoxifen (T) compared to placebo (P), after adjuvant chemotherapy (CT), in premenopausal women with early breast cancer (EBC): interim results of NCIC-CTG MA.12. [Abstract] J Clin Oncol 25 (Suppl 18): A-547, 2007.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

CMF regimen; Cyclophosphamide; Doxorubicin; Epirubicin; Fluorouracil; Methotrexate; Tamoxifen; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Therapeutics

Study Officials

• Vivien HC Bramwell, MB, BS, PhD, FRCP

  London Health Sciences Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: July 29, 2004
• Study Start: July 20, 1993
• Primary Completion: March 7, 2007
• Study Completion: January 11, 2011
• Last Updated: April 1, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (48)