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Breast CancerPhase 3NCT00002542

Tamoxifen in Treating Women With High-Risk Breast Cancer

A Phase 3 study testing CMF regimen, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by NCIC Clinical Trials Group at 48 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages Up to 120 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
CMF regimen, cyclophosphamide and doxorubicin hydrochloride
Type of treatment
Surgery or procedure
How many people
672 participants
Where
48 sitesCanada
Study dates
20 Jul 1993to 11 Jan 2011
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 120 years
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

48 sites in 1 country.

48 sites in 1 country

Canada48 sites
  • The Royal Victoria Hospital

    Barrie, L4M 6M2

  • William Osler Health Centre, Brampton Memorial

    Brampton, L6R 3J7

  • Tom Baker Cancer Centre

    Calgary, T2N 4N2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, C1A 8T5

  • Cross Cancer Institute

    Edmonton, T6G 1Z2

  • Regional Cancer Program of the Hopital Regional

    Greater Sudbury, P3E 5J1

  • QEII Health Sciences Center

    Halifax, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, L8V 5C2

  • Centre Hospitalier Regional de Lanaudiere

    Joliette, J6E 6J2

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, K7L 5P9

  • L'Hotel-Dieu de Levis

    Lévis, G6V 3Z1

  • London Regional Cancer Program

    London, N6A 4L6

  • Credit Valley Hospital

    Mississauga, L5M 2N1

  • CHUM - Hopital Notre-Dame

    Montreal, H2L 4M1

  • McGill University - Dept. Oncology

    Montreal, H2W 1S6

  • CHUM - Hotel Dieu du Montreal

    Montreal, H2W 1T8

  • CHUM - Pavillon Saint-Luc

    Montreal, H3X 3J4

  • Stronach Regional Health Centre at Southlake

    Newmarket, L3Y 2P9

  • Lakeridge Health Oshawa

    Oshawa, L1G 2B9

  • Ottawa Health Research Institute - General Division

    Ottawa, K1H 8L6

  • Penticton Regional Hospital

    Penticton, V2A 3G6

  • Peterborough Regional Health Centre

    Peterborough, K9H 7B6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, G1R 2J6

  • CHA-Hopital Du St-Sacrement

    Québec, G1S 4L8

  • University Institute of Cardiology and

    Québec, G1V 4G5

  • Allan Blair Cancer Centre

    Regina, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, P6A 2C4

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, J1H 5N4

  • Niagara Health System

    St. Catharines, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

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

  • BCCA - Fraser Valley Cancer Centre

    Surrey, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, P7B 6V4

  • Toronto East General Hospital

    Toronto, M4C 3E7

  • Odette Cancer Centre

    Toronto, M4N 3M5

  • St. Michael's Hospital

    Toronto, M5B 1W8

  • Mount Sinai Hospital

    Toronto, M5G 1X5

  • Univ. Health Network-The Toronto General Hospital

    Toronto, M5G 2C4

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, M5G 2M9

  • Women's College Hospital

    Toronto, M5S 1B2

  • St. Joseph's Health Centre

    Toronto, M6R 1B5

  • Trillium Health Centre - West Toronto

    Toronto, M9C 1A5

  • Humber River Regional Hospital

    Toronto, M9N 1N8

  • BCCA - Vancouver Cancer Centre

    Vancouver, V5Z 4E6

  • BCCA - Vancouver Island Cancer Centre

    Victoria, V8R 6V5

  • Windsor Regional Cancer Centre

    Windsor, N8W 2X3

  • CancerCare Manitoba

    Winnipeg, R3E 0V9

Other trials in Canada

About this study

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

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.

Read the detailed 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.

Conditions
Breast Cancer
Being tested
CMF regimen, cyclophosphamide, doxorubicin hydrochloride, epirubicin hydrochloride, fluorouracil
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2004 (estimated)
  2. Study start20 Jul 1993
  3. Primary completion7 Mar 2007
  4. Study completion11 Jan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
672 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00002542
Sponsor's protocol ID
MA12
Other IDs
CAN-NCIC-MA12, NCI-V93-0323, CDR0000063224
Status last verified
Mar 2020
First submitted
1 Nov 1999
Last updated
1 Apr 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CMF regimen, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by NCIC Clinical Trials Group at 48 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00002542, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2020.

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