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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Southwest Oncology Group
Cancer and Leukemia Group B
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00754845
First received: September 17, 2008
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of contralateral breast cancer [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]
  • Quality of life (QOL) as assessed by SF-36 Health Survey and the Menopause-Specific QOL Questionnaire (NCIC CTG participating centers) [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Enrollment: 1918
Study Start Date: October 2004
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: letrozole
Given orally
Other Name: femara
Placebo Comparator: 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.
Other: placebo
Given orally
Other Name: sugar pill

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  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: NCT00754845

  Show 43 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Southwest Oncology Group
Cancer and Leukemia Group B
Investigators
Study Chair: Paul E. Goss, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00754845     History of Changes
Other Study ID Numbers: MA17R, CAN-NCIC-MA17R, CDR0000614819
Study First Received: September 17, 2008
Last Updated: February 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

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

ClinicalTrials.gov processed this record on August 28, 2014