Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy

NCT00754845 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: MA17RCAN-NCIC-MA17RCDR0000614819
• Study Type: interventional
• Target: 1,918
• Locations: 2 countries
• Sites: 43

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating in women with breast cancer who have already received 5 years of aromatase inhibitor therapy. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.

  Unitil the end of study with a median follow up of 75 months

Secondary Outcomes (3)

• Incidence of Contralateral Breast Cancer

  10 years

• Overall Survival (OS)

  Until the end of study with a median follow-up of 75 months

• Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey

  8 years

Study Arms (2)

Letrozole

EXPERIMENTAL

Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Drug: letrozole

Placebo

PLACEBO COMPARATOR

Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Other: placebo

Interventions

letrozole DRUG

Given orally

Also known as: femara

Letrozole

placebo OTHER

Given orally

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 0 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Previously diagnosed with primary breast cancer * Must have received 4½ - 6 years of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane), either as initial therapy or after prior tamoxifen citrate, including treatment received as part of clinical trial CAN-NCIC-MA17 * Completed aromatase inhibitor therapy ≤ 2 years ago * No metastatic or recurrent disease, contralateral breast cancer, or ductal carcinoma in situ in either breast, as determined by the following: * Clinical examination of the breast area, axillae, and neck within the past 60 days * Mammogram within the past 12 months\* * Chest x-ray within the past 60 days * Bone scan, if alkaline phosphatase \> 2 times normal and/or there are symptoms of metastatic disease AND confirmatory x-ray, if bone scan results are questionable, within the past 60 days * Abdominal ultrasound, liver scan, or CT scan of the abdomen within the past 60 days, if ALT, AST, or alkaline phosphatase \> 2 times normal NOTE: \*A baseline mammogram is not required for patients who have undergone bilateral complete mastectomy * Hormone-receptor status: * Estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) primary tumor at the time of diagnosis, defined as a tumor receptor content of \> 10 fmol/mg protein or receptor positive by immunocytochemical assay (for patients not previously enrolled on clinical trial CAN-NCIC-MA17) * ER+ and/or PR+ primary tumor OR hormone receptor status of primary tumor unknown (for patients previously enrolled on clinical trial CAN-NCIC-MA17) PATIENT CHARACTERISTICS: * Menopausal status not specified * ECOG performance status 0-2 * Life expectancy ≥ 5 years * WBC \> 3.0 x 10\^9/L OR granulocyte count (polymorphs + bands) ≥ 1.5 times 10\^9/L * Platelet count \> 100 x 10\^9/L * AST and/or ALT \< 2 times upper limit of normal (ULN)\* * Alkaline phosphatase \< 2 times ULN\* * Able (i.e. sufficiently fluent) and willing to complete quality-of-life questionnaires in either English or French (NCIC CTG participating centers) * Inability to complete questionnaires due to illiteracy in English or French, loss of sight, or other equivalent reason allowed * Accessible for treatment and follow-up * No other prior or concurrent malignancy except adequately treated, superficial squamous cell or basal cell skin cancer, carcinoma in situ of the cervix, or other cancer treated \> 5 years ago that is presumed cured NOTE: \*Elevated levels allowed provided imaging examinations have ruled out metastatic disease PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No concurrent selective estrogen receptor modulator (e.g., raloxifene, idoxifene) * No other concurrent anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Eastern Cooperative Oncology Group: collaborator
• North Central Cancer Treatment Group: collaborator
• SWOG Cancer Research Network: collaborator
• Alliance for Clinical Trials in Oncology: collaborator

Study Sites (43)

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

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

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

St. Joseph's Health Centre

Toronto, Ontario, M6R 1B5, Canada

Location

Trillium Health Centre - West Toronto

Toronto, Ontario, M9C 1A5, Canada

Location

Humber River Regional Hospital

Toronto, Ontario, M9N 1N8, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Centre de Sante et de services sociaux de Gatineau

Gatineau, Quebec, J8P 7H2, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

L'Hotel-Dieu de Levis

Lévis, Quebec, G6V 3Z1, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUM - Hotel Dieu du Montreal

Montreal, Quebec, H2W 1T8, Canada

Location

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Related Publications (4)

• Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR. Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. N Engl J Med. 2016 Jul 21;375(3):209-19. doi: 10.1056/NEJMoa1604700. Epub 2016 Jun 5.

  PMID: 27264120 RESULT

• Li Y, Zheng X, Tu D, Ingle JN, Goss PE, Parulekar WR, Qin G. Predicting the clinical outcomes and benefit from letrozole after 5 years of treatment with aromatase inhibitors for early breast cancer: analysis from CCTG MA.17R. Breast Cancer Res Treat. 2022 Feb;191(3):523-533. doi: 10.1007/s10549-021-06448-5. Epub 2021 Nov 26.

  PMID: 34825307 DERIVED

• Ethier JL, Anderson GM, Austin PC, Clemons M, Parulekar W, Shepherd L, Summers Trasiewicz L, Tu D, Amir E. Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R. Eur J Cancer. 2021 May;149:117-127. doi: 10.1016/j.ejca.2021.02.034. Epub 2021 Apr 11.

  PMID: 33853037 DERIVED

• Lemieux J, Brundage MD, Parulekar WR, Goss PE, Ingle JN, Pritchard KI, Celano P, Muss H, Gralow J, Strasser-Weippl K, Whelan K, Tu D, Whelan TJ. Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years. J Clin Oncol. 2018 Feb 20;36(6):563-571. doi: 10.1200/JCO.2017.75.7500. Epub 2018 Jan 12.

  PMID: 29328860 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Sugars

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Senior Biostatistician
• Organization: Canadian Cancer Trials Group

dtu@ctg.queensu.ca

6135336430

Study Officials

• Paul E. Goss, MD, PhD

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2008
• First Posted: September 18, 2008
• Study Start: November 23, 2004
• Primary Completion: December 21, 2015
• Study Completion: April 19, 2017
• Last Updated: August 25, 2023
• Results First Posted: November 19, 2018

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); CA (42)