Letrozole in Treating Women With Primary Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy

Condition(s) targeted: Breast Cancer

Intervention: letrozole (Drug); placebo (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: NCIC Clinical Trials Group

Official(s) and/or principal investigator(s):
Paul E. Goss, MD, PhD, Study Chair, Affiliation: Massachusetts General Hospital

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.

Official title: A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed With Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in The MA.17 Study)

Study design: Treatment, Randomized, Double-Blind, Placebo Control

Primary outcome: Disease-free survival

Secondary outcome:

Incidence of contralateral breast cancer

Overall survival

Long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality, changes in bone mineral density, incidence of all bone fractures, and common toxicities

Quality of life (QOL) as assessed by SF-36 Health Survey and the Menopause-Specific QOL Questionnaire (NCIC CTG participating centers)

Detailed description: OBJECTIVES:

Primary

- To compare the disease-free survival of women with primary breast cancer treated with

letrozole vs placebo after completing approximately 5 years (i. e., 4½ - 6 years) of

aromatase inhibitor therapy (e. g., letrozole, anastrozole, or exemestane).

Secondary

- To compare the effect of these drugs on overall (all cause specific) mortality of these

patients.

- To compare the incidence of contralateral breast cancer in patients treated with these

drugs.

- To evaluate the long-term clinical and laboratory safety of aromatase inhibitor

therapy, particularly cardiovascular morbidity and mortality (e. g., significant coronary artery disease, including myocardial infarction and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths); incidence of all bone fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis); changes in bone density; and common toxicities.

- To compare overall quality of life (QOL) and menopausal-specific QOL of patients

treated with these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs < 2 years

vs 2 - 4½ years vs > 4½ years). Patients are randomized to 1 of 2 treatment arms.

- Arm I: 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.

- Arm II: 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.

Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months.

After completion of study therapy, patients are followed annually.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

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

BCCA - Fraser Valley Cancer Centre, Surrey, British Columbia V3V 1Z2, Canada; Recruiting
Gary K. Pansegrau, Phone: 604-930-4064

British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna, British Columbia V1Y 5L3, Canada; Recruiting
Susan Ellard, Phone: 250-712-3922

British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver, British Columbia V5Z 4E6, Canada; Recruiting
Stephen Chia, Phone: 604-877-6000

British Columbia Cancer Agency - Vancouver Island Centre, Victoria, British Columbia V8R 6V5, Canada; Recruiting
Sharon Allan, Phone: 250-519-5570

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Recruiting
Andrew L. Cooke, Phone: 204-787-1458

Doctor Leon Richard Oncology Centre, Moncton, New Brunswick E1C 8X3, Canada; Recruiting
Pierre Whitlock, Phone: 506-862-4030

Moncton Hospital, Moncton, New Brunswick E1C 6Z8, Canada; Recruiting
Sheldon Rubin, Phone: 506-857-2881

Saint John Regional Hospital, Saint John, New Brunswick E2L 4L2, Canada; Recruiting
S. Eshwar Kumar, Phone: 506-648-6884

Doctor H. Bliss Murphy Cancer Centre, St. John's, Newfoundland and Labrador AIB 3V6, Canada; Recruiting
Kara Laing, Phone: 709-777-8095

Nova Scotia Cancer Centre, Halifax, Nova Scotia B3H 1V7, Canada; Recruiting
Daniel Rayson, Phone: 902-473-6106

Algoma District Cancer Program at Sault Area Hospital, Sault Ste. Marie, Ontario P6A 2C4, Canada; Recruiting
David Walde, Phone: 705-759-3815

Cancer Care Program at Thunder Bay Regional Health Sciences, Thunder Bay, Ontario P7B 6V4, Canada; Recruiting
Dimitrios Vergidis, Phone: 807-684-7204

Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 5P9, Canada; Recruiting
Wendy Shelley, Phone: 613-544-2630

Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital, Mississauga, Ontario L5M 2N1, Canada; Recruiting
Robert Myers, Phone: 905-813-1100

Edmond Odette Cancer Centre at Sunnybrook, Toronto, Ontario M4N 3M5, Canada; Recruiting
Kathleen I. Pritchard, Phone: 416-480-4616

Humber River Regional Hospital - Weston, Toronto, Ontario M9N 1N8, Canada; Recruiting
Jonathan J. Wilson, Phone: 416-249-4367

London Regional Cancer Program at London Health Sciences Centre, London, Ontario N6A 4L6, Canada; Recruiting
Francisco Perera, Phone: 519-685-8500

Margaret and Charles Juravinski Cancer Centre, Hamilton, Ontario L8V 5C2, Canada; Recruiting
Richard G. Tozer, Phone: 905-387-9495

Mount Sinai Hospital - Toronto, Toronto, Ontario M5G 1X5, Canada; Recruiting
Martin Blackstein, Phone: 416-586-5371

North York General Hospital - Ontario, Toronto, Ontario M2K 1E1, Canada; Recruiting
Vivian Glenns, Phone: 416-498-4888

Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario P3E 5J1, Canada; Recruiting
Pedro G. Lopez, Phone: 705-522-6237

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
David Warr, Phone: 416-946-2260

R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa, Oshawa, Ontario L1G 2B9, Canada; Recruiting
Jose Chang, Phone: 905-576-8711

Southlake Regional Health Centre, Newmarket, Ontario L3Y 2P9, Canada; Recruiting
Farrah Kassam, Phone: -

St. Catharines General Hospital at Niagara Health System, St. Catharines, Ontario L2R 7C6, Canada; Recruiting
Brian Findlay, Phone: 905-684-7271

St. Joseph's Health Centre - Toronto, Toronto, Ontario M6R 1B5, Canada; Recruiting
Murray Davidson, Phone: 416-766-2365

St. Michael's Hospital - Toronto, Toronto, Ontario M5B 1W8, Canada; Recruiting
Rashida Haq, Phone: 416-864-5912

Toronto East General Hospital, Toronto, Ontario M4C 3E7, Canada; Recruiting
Yasmin H. Rahim, Phone: 416-469-3325

Trillium Health Centre - Mississauga Site, Toronto, Ontario M9C 1A5, Canada; Recruiting
John A.P. Gapski, Phone: 416-521-4118

Windsor Regional Cancer Centre at Windsor Regional Hospital, Windsor, Ontario N8W 2X3, Canada; Recruiting
Caroline Hamm, Phone: 519-253-5253

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital, Charlottetown, Prince Edward Island C1A 8T5, Canada; Recruiting
Dagny Dryer, Phone: 902-894-2027

CHUM - Hotel Dieu Hospital, Montreal, Quebec H2W 1T8, Canada; Recruiting
Claude Potvin, Phone: 514-890-8000

CHUS-Hopital Fleurimont, Sherbrooke, Quebec J1H 5N4, Canada; Recruiting
Abdenour Nabid, Phone: 819-346-1110

Hopital Charles Lemoyne, Greenfield Park, Quebec J4V 2H1, Canada; Recruiting
Jean Latreille, Phone: 450-466-5009

Hopital du Saint-Sacrement - Quebec, Quebec City, Quebec G1S 4L8, Canada; Recruiting
Jean Robert, Phone: 418-682-7511

Hotel-Dieu de Levis, Levis, Quebec G6V 3Z1, Canada; Recruiting
Felix Couture, Phone: 418-691-5225

Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Recruiting
Pierre Dube, Phone: 514-252-3822

McGill Cancer Centre at McGill University, Montreal, Quebec H2W 1S6, Canada; Recruiting
Francois Patenaude, Phone: 514-934-1934

Allan Blair Cancer Centre at Pasqua Hospital, Regina, Saskatchewan S4T 7T1, Canada; Recruiting
Haji Ibrahim Chalchal, Phone: 306-766-2691

Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada; Recruiting
Ali El-Gayed, Phone: 306-655-2739

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2004
Last updated: May 21, 2009