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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)


Phase 3
N/A
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

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)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Disease-free survival

Outcome Time Frame:

8 years

Safety Issue:

No

Principal Investigator

Paul E. Goss, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Massachusetts General Hospital

Authority:

Canada: Health Canada

Study ID:

MA17R

NCT ID:

NCT00754845

Start Date:

October 2004

Completion Date:

May 2015

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Breast Neoplasms

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