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Letrozole After Tamoxifen in Treating Women With Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: November 1, 1999   Last Updated: August 11, 2009   History of Changes
Sponsors and Collaborators: NCIC Clinical Trials Group
National Cancer Institute (NCI)
North Central Cancer Treatment Group
International Breast Cancer Study Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
European Organization for Research and Treatment of Cancer
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003140
  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 III

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
Official Title: A Phase III Randomized Double Blind Study of Vorozole 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 National Cancer Institute (NCI):

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

Estimated Enrollment: 4700
Study Start Date: August 1998
Estimated Primary Completion Date: September 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
Patients receive oral letrozole once daily.
Drug: letrozole
Given orally
Arm II: Placebo Comparator
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003140

  Show 542 Study Locations
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 Organization for Research and Treatment of Cancer
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, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10.
Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Goss PE. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Ann Oncol. 2008 Mar 10; [Epub ahead of print]
Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, Toxicity, and Quality of Life in Older Women With Early-Stage Breast Cancer Treated With Letrozole or Placebo After 5 Years of Tamoxifen: NCIC CTG Intergroup Trial MA.17. J Clin Oncol. 2008 Mar 10; [Epub ahead of print]
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 PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Efficacy of Letrozole Extended Adjuvant Therapy According to Estrogen Receptor and Progesterone Receptor Status of the Primary Tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J Clin Oncol. 2007 Apr 23; [Epub ahead of print]
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 JN, Tu D, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Goss PE. Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Res Treat. 2006 Oct;99(3):295-300. Epub 2006 Mar 16.
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.
Perez EA, Josse RG, Pritchard KI, Ingle JN, Martino S, Findlay BP, Shenkier TN, Tozer RG, Palmer MJ, Shepherd LE, Liu S, Tu D, Goss PE. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol. 2006 Aug 1;24(22):3629-35. Epub 2006 Jul 5.
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, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71.
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.
Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12.
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.
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9.
Baum M. Adjuvant endocrine therapy in postmenopausal women with early breast cancer: where are we now? Eur J Cancer. 2005 Aug;41(12):1667-77. Review.
Baum M. Current Status of Aromatase Inhibitors in the Management of Breast Cancer and Critique of the NCIC MA-17 Trial. Cancer Control. 2004 Jul-Aug;11(4):217-21.
Booth CM, Pater JL, Goss PE. Identifying breast cancer patients most likely to benefit from aromatase inhibitor therapy after adjuvant tamoxifen. Cancer. 2007 Mar 12;109(9):1927-1928 [Epub ahead of print]
Buzdar A, Chlebowski R, Cuzick J, Duffy S, Forbes J, Jonat W, Ravdin P. Defining the role of aromatase inhibitors in the adjuvant endocrine treatment of early breast cancer. Curr Med Res Opin. 2006 Aug;22(8):1575-85. Review.
Scott LJ, Keam SJ. Letrozole : in postmenopausal hormone-responsive early-stage breast cancer. Drugs. 2006;66(3):353-62. Review.
Vakaet L. Re: Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2006 Aug 16;98(16):1162; author reply 1162-3. No abstract available.
Wardley AM. Emerging data on optimal adjuvant endocrine therapy: Breast International Group trial 1-98/MA.17. Clin Breast Cancer. 2006 Feb;6 Suppl 2:S45-50. Review.

Study ID Numbers: CDR0000065921, 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
Study First Received: November 1, 1999
Last Updated: August 11, 2009
ClinicalTrials.gov Identifier: NCT00003140     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Study placed in the following topic categories:
Skin Diseases
Adjuvants, Immunologic
Breast Neoplasms
Letrozole
Aromatase Inhibitors
Tamoxifen
Breast Diseases

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

ClinicalTrials.gov processed this record on September 02, 2009