Tamoxifen in Treating Women With High-Risk Breast Cancer

Breast Cancer Clinical Trial

Official title:

Double-Blind Randomized Trial of Tamoxifen Versus Placebo in Patients With Node Positive or High Risk Node Negative Breast Cancer Who Have Completed CMF, CEF, or AC Adjuvant Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002542
• Other study ID #: MA12
• Secondary ID: CAN-NCIC-MA12NCI
• Status: Completed
• Phase: Phase 3
• Start date: July 20, 1993
• Est. completion date: January 11, 2011

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 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 672
• Est. completion date: January 11, 2011
• Est. primary completion date: March 7, 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• CMF regimen

• cyclophosphamide

• doxorubicin hydrochloride

• epirubicin hydrochloride

• fluorouracil

• methotrexate

• tamoxifen citrate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	The Royal Victoria Hospital	Barrie
Canada	William Osler Health Centre, Brampton Memorial	Brampton
Canada	Tom Baker Cancer Centre	Calgary
Canada	PEI Cancer Treatment Centre,Queen Elizabeth Hospital	Charlottetown
Canada	Cross Cancer Institute	Edmonton
Canada	QEII Health Sciences Center	Halifax
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton
Canada	Centre Hospitalier Regional de Lanaudiere	Joliette
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston
Canada	L'Hotel-Dieu de Levis	Levis
Canada	London Regional Cancer Program	London
Canada	Credit Valley Hospital	Mississauga
Canada	CHUM - Hopital Notre-Dame	Montreal
Canada	CHUM - Hotel Dieu du Montreal	Montreal
Canada	CHUM - Pavillon Saint-Luc	Montreal
Canada	McGill University - Dept. Oncology	Montreal
Canada	Stronach Regional Health Centre at Southlake	Newmarket
Canada	Lakeridge Health Oshawa	Oshawa
Canada	Ottawa Health Research Institute - General Division	Ottawa
Canada	Penticton Regional Hospital	Penticton
Canada	Peterborough Regional Health Centre	Peterborough
Canada	University Institute of Cardiology and	Quebec
Canada	CHA-Hopital Du St-Sacrement	Quebec City
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City
Canada	Allan Blair Cancer Centre	Regina
Canada	Atlantic Health Sciences Corporation	Saint John
Canada	Saskatoon Cancer Centre	Saskatoon
Canada	Algoma District Cancer Program	Sault Ste. Marie
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke
Canada	Niagara Health System	St. Catharines
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Regional Cancer Program of the Hopital Regional	Sudbury
Canada	BCCA - Fraser Valley Cancer Centre	Surrey
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay
Canada	Humber River Regional Hospital	Toronto
Canada	Mount Sinai Hospital	Toronto
Canada	Odette Cancer Centre	Toronto
Canada	St. Joseph's Health Centre	Toronto
Canada	St. Michael's Hospital	Toronto
Canada	Toronto East General Hospital	Toronto
Canada	Trillium Health Centre - West Toronto	Toronto
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto
Canada	Univ. Health Network-The Toronto General Hospital	Toronto
Canada	Women's College Hospital	Toronto
Canada	BCCA - Vancouver Cancer Centre	Vancouver
Canada	BCCA - Vancouver Island Cancer Centre	Victoria
Canada	Windsor Regional Cancer Centre	Windsor
Canada	CancerCare Manitoba	Winnipeg

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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.

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).