Letrozole After Tamoxifen in Treating Women With Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
International Breast Cancer Study Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00003140
First received: November 1, 1999
Last updated: September 18, 2014
Last verified: March 2012
  Purpose

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Double Blind Study of Letrozole Versus Placebo in Women With Primary Breast Cancer Completing Five or More Years of Adjuvant Tamoxifen

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 5187
Study Start Date: August 1998
Study Completion Date: October 2003
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral letrozole once daily.
Drug: letrozole
Given orally
Other Name: Femara
Placebo Comparator: Arm II
Patients receive oral placebo once daily.
Other: placebo
Given orally

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary invasive breast carcinoma resected at time of original diagnosis

    • No ductal carcinoma in situ
  • Axillary lymph node negative, positive, or unknown
  • No evidence of metastases
  • No localized or distant breast cancer recurrence
  • Not registered on protocol NCCTG-893052, any other IBCSG protocol, or protocol SWOG-S9623
  • Hormone receptor status:

    • Estrogen or progesterone receptor positive as defined by tumor receptor content at least 10 fmol/mg protein or receptor positive by ERICA or PgRICA
    • Unknown status allowed if effort to determine status has been made by immunocytochemistry
  • No contralateral breast cancer

PATIENT CHARACTERISTICS:

Age:

  • Postmenopausal

Sex:

  • Female

Menopausal status:

  • Postmenopausal defined by one of the following:

    • Age 50 or over at start of adjuvant tamoxifen
    • Under age 50 and considered postmenopausal by treating physician at start of adjuvant tamoxifen
    • Under age 50 at start of adjuvant tamoxifen and had bilateral oophorectomy (surgical or radiation)
    • Under age 50 and premenopausal at start of adjuvant tamoxifen, but became amenorrheic during tamoxifen and remained amenorrheic for at least 1 year
    • Considered postmenopausal by physician with LH/FSH levels under the treatment center's postmenopausal limits

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 5 years

Hematopoietic:

  • WBC ≥ 3,000/mm^3 OR
  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic:

  • AST and/or ALT < 2 times upper limit of normal (ULN) (unless imaging examinations have ruled out metastatic disease)
  • Alkaline phosphatase < 2 times ULN (unless imaging examinations have ruled out metastatic disease)

Renal:

  • Not specified

Other:

  • No concurrent medical or psychiatric condition that would preclude study participation
  • No other malignancy within the past 5 years except adequately treated superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
  • Able to swallow study drug
  • Adequate oral intake

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Prior adjuvant chemotherapy allowed
  • No concurrent chemotherapy

Endocrine therapy:

  • Completed at least 4.5 but no more than 6 years of adjuvant tamoxifen after resection
  • Completed at least 4.5-6 years of adjuvant aromatase inhibitor as initial therapy or after tamoxifen
  • No more than 3 months since prior adjuvant tamoxifen
  • No concurrent hormone replacement therapy (e.g., megestrol)
  • No concurrent selective estrogen-receptor modulators (e.g., raloxifene or idoxifene)
  • Concurrent intermittent vaginal estrogens (e.g., Estring) allowed if other local measures for intractable vaginal atrophy are insufficient
  • No other concurrent aromatase inhibitors
  • No more than 2 years since prior aromatase inhibitor therapy (re-randomization)

Radiotherapy:

  • Prior radiotherapy allowed

Surgery:

  • See Disease Characteristics

Other:

  • At least 1 month since prior investigational drugs
  • Prior treatment on a clinical trial for breast cancer allowed if permission has been obtained from the sponsors of the original study for their patient to participate on MA.17/JMA.17/BIG-97-01
  • No prior placebo on core protocol
  • No concurrent anticancer therapy
  • Concurrent thyroid medication, calcium, vitamin D, and bisphosphonates allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003140

  Hide Study Locations
Locations
Canada, Alberta
Lethbridge Cancer Centre
Lethbridge, Alberta, Canada, T1J 1W5
Canada, British Columbia
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
NRGH - Nanaimo Cancer Clinic
Nanaimo, British Columbia, Canada, V9S 2B7
Penticton Regional Hospital
Penticton, British Columbia, Canada, V2A 3G6
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
BCCA - Vancouver Island Cancer Centre
Victoria, British Columbia, Canada, V8R 6V5
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Vitalite Health Network - Dr. Leon Richard
Moncton, New Brunswick, Canada, E1C 8X3
The Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Atlantic Health Sciences Corporation
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, AIB 3V6
Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
The Royal Victoria Hospital
Barrie, Ontario, Canada, L4M 6M2
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Markham Stouffville Hospital
Markham, Ontario, Canada, L6B 1A1
Credit Valley Hospital
Mississauga, Ontario, Canada, L5M 2N1
Stronach Regional Health Centre at Southlake
Newmarket, Ontario, Canada, L3Y 2P9
Lakeridge Health Oshawa
Oshawa, Ontario, Canada, L1G 2B9
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Peterborough Regional Health Centre
Peterborough, Ontario, Canada, K9H 7B6
Algoma District Cancer Program
Sault Ste. Marie, Ontario, Canada, P6B 0A8
Niagara Health System
St. Catharines, Ontario, Canada, L2R 7C6
Regional Cancer Program of the Hopital Regional
Sudbury, Ontario, Canada, P3E 5J1
Thunder Bay Regional Health Science Centre
Thunder Bay, Ontario, Canada, P7B 6V4
North York General Hospital
Toronto, Ontario, Canada, M2K 1E1
Univ. Health Network-The Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Humber River Regional Hospital
Toronto, Ontario, Canada, M9N 1N8
St. Joseph's Health Centre
Toronto, Ontario, Canada, M6R 1B5
Trillium Health Centre - West Toronto
Toronto, Ontario, Canada, M9C 1A5
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Toronto East General Hospital
Toronto, Ontario, Canada, M4C 3E7
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Windsor Regional Cancer Centre
Windsor, Ontario, Canada, N8W 2X3
Canada, Prince Edward Island
PEI Cancer Treatment Centre,Queen Elizabeth Hospital
Charlottetown, Prince Edward Island, Canada, C1A 8T5
Canada, Quebec
Centre de Sante et de services sociaux de Gatineau
Gatineau, Quebec, Canada, J8P 7H2
L'Hotel-Dieu de Levis
Levis, Quebec, Canada, G6V 3Z1
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
CHUM - Pavillon Saint-Luc
Montreal, Quebec, Canada, H3X 3J4
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
CHUM - Hotel Dieu du Montreal
Montreal, Quebec, Canada, H2W 1T8
CHUQ-Pavillon Hotel-Dieu de Quebec
Quebec City, Quebec, Canada, G1R 2J6
CHA-Hopital Du St-Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
University Institute of Cardiology and
Quebec, Canada, G1V 4G5
United Kingdom
The Royal Marsden NHS Foundation Trust
London, United Kingdom, SW3 6JJ
Christie's Hospital NHS Trust
Manchester, United Kingdom, M2O 4BX
Wythenshawe Hospital
Manchester, United Kingdom, M23 9LT
The Royal Marsden NHS Foundation Trust - Sutton
Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
NCIC Clinical Trials Group
North Central Cancer Treatment Group
International Breast Cancer Study Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Paul E. Goss, MD, PhD Massachusetts General Hospital
Study Chair: James N. Ingle, MD Mayo Clinic
Study Chair: Monica Castiglione-Gertsch, MD University Hospital Inselspital, Berne
Study Chair: Nicholas J. Robert, MD Fairfax Northern Virginia Hematology Oncology, PC - Fairfax
Study Chair: Silvana Martino, DO John Wayne Cancer Institute at Saint John's Health Center
Study Chair: Hyman B. Muss, MD University of Vermont
Study Chair: Martine J. Piccart-Gebhart, MD, PhD Institut Jules Bordet
  More Information

Additional Information:
Publications:
Goss PE, Ingle JN, Martino S, et al.: Outcomes of women who were premenopausal at diagnosis of early stage breast cancer in the NCIC CTG MA17 trial. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-13, 2009.
Chapman JW, Meng D, Shepherd L, et al.: Competing causes of death in breast cancer extended adjuvant endocrine therapy: NCIC CTG MA.17. [Abstract] American Society of Clinical Oncology 2007 Breast Cancer Symposium, 7-8 September 2007, San Francisco, California A-56, 2007.
Goss P: Breaking the 5-year barrier: results from the MA.17 extended adjuvant trial in women who have completed adjuvant tamoxifen treatment. [Abstract] European Journal of Cancer Supplements 4 (9): 10-5, 2006.
Ingle J, Tu D, Shepherd L, et al.: NCIC CTG MA.17: intent to treat analysis (ITT) of randomized patients after a median follow-up of 54 months. [Abstract] J Clin Oncol 24 (Suppl 18): A-549, 2006.
Moy B, Tu D, Shepherd LE, et al.: NCIC CTG MA.17: tolerability of letrozole among ethnic minority women. [Abstract] J Clin Oncol 24 (Suppl 18): A-6018, 305s, 2006.
Pater JL, Tu D, Ingle JN, et al.: An evaluation of the early termination (ET) of MA.17 extended adjuvant therapy trial. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2081, S107-8, 2006.
Robert NJ, Goss PE, Ingle JN, et al.: Updated analysis of NCIC CTG MA.17 (letrozole vs. placebo to letrozole vs placebo) post unblinding. [Abstract] J Clin Oncol 24 (Suppl 18): A-550, 2006.
Abetz L, Barghout V, Thomas S, et al.: Letrozole did not worsen quality of life relative to placebo in post-menopausal women with early breast cancer: results from the US subjects of the MA-17 study. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-2047, 2005.
Goss PE, Ingle JN, Palmer MJ, et al.: Updated analysis of NCIC CTG MA.17 (letrozole vs. placebo to letrozole vs placebo) post unblinding. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-16, 2005.
Goss PE, Ingle JN, Tu D: NCIC CTG MA17: disease free survival according to estrogen receptor and progesterone receptor status of the primary tumor. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-2042, 2005.
Ingle JN, Goss PE, Tu D: Analysis of duration of letrozole extended adjuvant therapy as measured by hazard ratios of disease recurrence over time for patients on NCIC CTG MA.17. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-17, 2005.
Luk C, Goss P, Pritchard K, et al.: Determinants of preferences for starting extended adjuvant letrozole (L) in postmenopausal women following five years of tamoxifen. [Abstract] J Clin Oncol 23 (Suppl 16): A-642, 39s, 2005.
Vachon CM, Ingle JN, Scott CG, et al.: Pilot study of changes in mammographic density in women treated with letrozole or placebo on NCIC CTG MA17. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-6005, 2005.
Goss PE, Ingle JN, Martino S, et al.: Updated analysis of the NCIC CTG MA.17 randomized placebo (P) controlled trial of letrozole (L) after five years of tamoxifen in postmenopausal women with early stage breast cancer. [Abstract] J Clin Oncol 22 (Suppl 14): A-847, 88s, 2004.
Whelan T, Goss P, Ingle J, et al.: Assessment of quality of life (QOL) in MA.17, a randomized placebo-controlled trial of letrozole in postmenopausal women following five years of tamoxifen. [Abstract] J Clin Oncol 22 (Suppl 14): A-517, 7s, 2004.

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00003140     History of Changes
Other Study ID Numbers: MA17, U10CA025224, CAN-NCIC-MA17, CALGB-49805, E-JMA17, EORTC-10983, IBCSG-BIG97-01, NCCTG-JMA17, SWOG-JMA17, JRF-Vor-Int-10, NCCTG-CAN-MA17, SWOG-CAN-MA17, CDR0000065921
Study First Received: November 1, 1999
Last Updated: September 18, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014