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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00754845
• Other study ID #: MA17R
• Secondary ID: CAN-NCIC-MA17RCD
• Status: Completed
• Phase: Phase 3
• Start date: November 23, 2004
• Est. completion date: April 19, 2017

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1918
• Est. completion date: April 19, 2017
• Est. primary completion date: December 21, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 0 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• letrozole
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
Canada	PEI Cancer Treatment Centre,Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Centre de Sante et de services sociaux de Gatineau	Gatineau	Quebec
Canada	Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	L'Hotel-Dieu de Levis	Levis	Quebec
Canada	London Regional Cancer Program	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick
Canada	CHUM - Hotel Dieu du Montreal	Montreal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Humber River Regional Hospital	Toronto	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	North York General Hospital	Toronto	Ontario
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	St. Joseph's Health Centre	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Trillium Health Centre - West Toronto	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United Kingdom	Wythenshawe Hospital	Manchester

Sponsors (5)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group, North Central Cancer Treatment Group, SWOG Cancer Research Network

Countries where clinical trial is conducted

Canada,  United Kingdom, 

References & Publications (1)

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 t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of Contralateral Breast Cancer	The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer	10 years
Secondary	Overall Survival (OS)	For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.	Until the end of study with a median follow-up of 75 months
Secondary	Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey	Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).	8 years