Tamoxifen in Treating Women With High-Risk Breast Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: CMF regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: fluorouracil Drug: methotrexate Drug: tamoxifen citrate Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: Double-Blind Primary Purpose: Treatment |
| Official Title: | DOUBLE-BLIND RANDOMIZED TRIAL OF TAMOXIFEN VERSUS PLACEBO IN PATIENTS WITH NODE POSITIVE BREAST CANCER WHO HAVE COMPLETED CMF, CEF OR AC ADJUVANT CHEMOTHERAPY |
| Estimated Enrollment: | 800 |
| Study Start Date: | July 1993 |
| Study Completion Date: | January 2011 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
OBJECTIVES: I. Compare the duration of overall survival and disease-free survival in premenopausal women with operable, high risk node negative or axillary node-positive breast cancer who have undergone complete surgical resection of all known disease by means of total or partial mastectomy, and have received standard adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF), cyclophosphamide, epirubicin, and fluorouracil (CEF), or doxorubicin and cyclophosphamide (AC) followed by either daily tamoxifen for 5 years or placebo. II. Compare the short- and long-term toxicity in patients receiving tamoxifen versus placebo. III. Monitor follicle-stimulating hormone, luteinizing hormone, and estradiol levels, and determine whether overall survival and disease-free survival are affected by hormonal or menopausal status during or at completion of adjuvant chemotherapy or during or after tamoxifen or placebo treatment in these patients.
OUTLINE: This is a randomized, double blind study. Patients are stratified by adjuvant chemotherapy regimen (cyclophosphamide, epirubicin, and fluorouracil vs cyclophosphamide, methotrexate, and fluorouracil vs cyclophosphamide and doxorubicin), hormone receptor status (ER and/or PR positive vs ER and PR negative), number of positive nodes (1-3 vs 4-9 vs 10 or more), and participating institution. Patients receive one of three regimens of adjuvant chemotherapy at the discretion of the investigator. Regimen A: Patients receive oral cyclophosphamide on days 1-14 and epirubicin IV and fluorouracil IV on days 1 and 8. Courses repeat every 28 days for a total of 6 courses. Following chemotherapy, lumpectomy patients receive local radiotherapy daily for 5 weeks. Regimen B: Patients receive oral cyclophosphamide on days 1-14 or cyclophosphamide IV on day 1 and 8, methotrexate on days 1 and 8, and fluorouracil IV on days 1 and 8. Courses repeat every 28 days for a total of 6 courses. Concurrent with or following chemotherapy, lumpectomy patients receive local radiotherapy daily for 5 weeks. Regimen C: Patients receive doxorubicin IV and cyclophosphamide IV every 21 days for a total of 4 courses. Following chemotherapy, lumpectomy patients receive local radiotherapy daily for 5 weeks. Patients are then randomized to receive either oral tamoxifen or a placebo once daily for 5 years, beginning within 6 weeks of completion of chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed for survival.
PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study over 4 years.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Hide Study Locations| Canada, Newfoundland and Labrador | |
| Dr. H. Bliss Murphy Cancer Centre | |
| St. John's, Newfoundland and Labrador, Canada, AIB 3V6 | |
| Canada | |
| The Royal Victoria Hospital | |
| Barrie, Canada, L4M 6M2 | |
| William Osler Health Centre, Brampton Memorial | |
| Brampton, Canada, L6R 3J7 | |
| Tom Baker Cancer Centre | |
| Calgary, Canada, T2N 4N2 | |
| PEI Cancer Treatment Centre,Queen Elizabeth Hospital | |
| Charlottetown, Canada, C1A 8T5 | |
| Cross Cancer Institute | |
| Edmonton, Canada, T6G 1Z2 | |
| QEII Health Sciences Center | |
| Halifax, Canada, B3H 1V7 | |
| Juravinski Cancer Centre at Hamilton Health Sciences | |
| Hamilton, Canada, L8V 5C2 | |
| Centre Hospitalier Regional de Lanaudiere | |
| Joliette, Canada, J6E 6J2 | |
| Cancer Centre of Southeastern Ontario at Kingston | |
| Kingston, Canada, K7L 5P9 | |
| L'Hotel-Dieu de Levis | |
| Levis, Canada, G6V 3Z1 | |
| London Regional Cancer Program | |
| London, Canada, N6A 4L6 | |
| Credit Valley Hospital | |
| Mississauga, Canada, L5M 2N1 | |
| CHUM - Pavillon Saint-Luc | |
| Montreal, Canada, H3X 3J4 | |
| CHUM - Hopital Notre-Dame | |
| Montreal, Canada, H2L 4M1 | |
| McGill University - Dept. Oncology | |
| Montreal, Canada, H2W 1S6 | |
| CHUM - Hotel Dieu du Montreal | |
| Montreal, Canada, H2W 1T8 | |
| Stronach Regional Health Centre at Southlake | |
| Newmarket, Canada, L3Y 2P9 | |
| Lakeridge Health Oshawa | |
| Oshawa, Canada, L1G 2B9 | |
| Ottawa Health Research Institute - General Division | |
| Ottawa, Canada, K1H 8L6 | |
| Penticton Regional Hospital | |
| Penticton, Canada, V2A 3G6 | |
| Peterborough Regional Health Centre | |
| Peterborough, Canada, K9H 7B6 | |
| University Institute of Cardiology and | |
| Quebec, Canada, G1V 4G5 | |
| CHUQ-Pavillon Hotel-Dieu de Quebec | |
| Quebec City, Canada, G1R 2J6 | |
| CHA-Hopital Du St-Sacrement | |
| Quebec City, Canada, G1S 4L8 | |
| Allan Blair Cancer Centre | |
| Regina, Canada, S4T 7T1 | |
| Atlantic Health Sciences Corporation | |
| Saint John, Canada, E2L 4L2 | |
| Saskatoon Cancer Centre | |
| Saskatoon, Canada, S7N 4H4 | |
| Algoma District Cancer Program | |
| Sault Ste. Marie, Canada, P6A 2C4 | |
| Centre hospitalier universitaire de Sherbrooke | |
| Sherbrooke, Canada, J1H 5N4 | |
| Niagara Health System | |
| St. Catharines, Canada, L2R 7C6 | |
| Regional Cancer Program of the Hopital Regional | |
| Sudbury, Canada, P3E 5J1 | |
| BCCA - Fraser Valley Cancer Centre | |
| Surrey, Canada, V3V 1Z2 | |
| Thunder Bay Regional Health Science Centre | |
| Thunder Bay, Canada, P7B 6V4 | |
| Mount Sinai Hospital | |
| Toronto, Canada, M5G 1X5 | |
| Humber River Regional Hospital | |
| Toronto, Canada, M9N 1N8 | |
| St. Joseph's Health Centre | |
| Toronto, Canada, M6R 1B5 | |
| St. Michael's Hospital | |
| Toronto, Canada, M5B 1W8 | |
| Toronto East General Hospital | |
| Toronto, Canada, M4C 3E7 | |
| Odette Cancer Centre | |
| Toronto, Canada, M4N 3M5 | |
| Trillium Health Centre - West Toronto | |
| Toronto, Canada, M9C 1A5 | |
| Univ. Health Network-Princess Margaret Hospital | |
| Toronto, Canada, M5G 2M9 | |
| Univ. Health Network-The Toronto General Hospital | |
| Toronto, Canada, M5G 2C4 | |
| Women's College Hospital | |
| Toronto, Canada, M5S 1B2 | |
| BCCA - Vancouver Cancer Centre | |
| Vancouver, Canada, V5Z 4E6 | |
| BCCA - Vancouver Island Cancer Centre | |
| Victoria, Canada, V8R 6V5 | |
| Windsor Regional Cancer Centre | |
| Windsor, Canada, N8W 2X3 | |
| CancerCare Manitoba | |
| Winnipeg, Canada, R3E 0V9 | |
| Study Chair: | Vivien H.C. Bramwell, MB, BS, PhD, FRCP | London Regional Cancer Program at London Health Sciences Centre |
More Information
Additional Information:
Publications:
| Responsible Party: | Ralph Meyer, M.D, NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00002542 History of Changes |
| Other Study ID Numbers: | MA12, CAN-NCIC-MA12, NCI-V93-0323, CDR0000063224 |
| Study First Received: | November 1, 1999 |
| Last Updated: | January 18, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by NCIC Clinical Trials Group:
|
stage I breast cancer stage II breast cancer stage IIIA breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Fluorouracil Methotrexate Doxorubicin Epirubicin Tamoxifen Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Antimetabolites Antimetabolites, Antineoplastic Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Dermatologic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013