Know Cancer

or
forgot password

A Randomized Phase III Trial Of Exemestane Versus Anastrozole In Postmenopausal Women With Receptor Positive Primary Breast Cancer


Phase 3
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

A Randomized Phase III Trial Of Exemestane Versus Anastrozole In Postmenopausal Women With Receptor Positive Primary Breast Cancer


OBJECTIVES:

Primary

- Compare the event-free survival of postmenopausal women with receptor-positive primary
breast cancer when treated with exemestane vs anastrozole.

Secondary

- Compare the overall survival of patients treated with these regimens.

- Compare the time to distant recurrence in patients treated with these regimens.

- Compare the incidence of new primary contralateral breast cancer in patients treated
with these regimens.

- Compare the incidence of all clinical fractures, specifically hip and vertebral
fractures, in patients treated with these regimens.

- Compare cardiovascular morbidity and mortality (i.e., significant coronary heart
disease, which includes myocardial infarctions and angina requiring percutaneous
transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal
strokes, and all vascular deaths) in patients treated with these regimens.

- Correlate therapy induced changes in breast density with plasma hormones and growth
factors, drug levels of exemestane and anastrozole, genetic variation and breast cancer
recurrence or contralateral events in patients treated with these regimens.

- Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph
node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes
vs no), and herceptin use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral exemestane (25 mg) once daily for 5 years.

- Arm II: Patients receive oral anastrozole (1 mg) once daily for 5 years. In both arms,
treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months during the first year of study participation and
annually thereafter.

PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed invasive breast cancer

- pT1-3; pNX, pN0-2 or pN3*; M0

- Neoadjuvant patients are eligible no earlier than 3 weeks or later than 3 months
after excisional surgery, provided both the clinical-diagnostic staging of
cancer and postsurgical resection-pathologic staging of cancer meet the
requirements for primary tumor, regional lymph nodes, and distant metastasis
classification NOTE: *Only when the sole basis for this classification is the
presence of 10 or more involved axillary lymph nodes

- Completely resected disease

- Primary surgery performed at least 3 weeks but no more than 3 months before
study entry (if no chemotherapy was given)

- Primary surgery is defined as the last surgery at which histologic evidence
of invasive or in situ disease was present in the pathology specimen

- Patients with positive sentinel lymph node biopsy are eligible provided they
have had a subsequent axillary lymph node dissection

- No metachronous breast cancer

- Bilateral mammogram within the past 12 months unless initial surgery was a total
mastectomy, in which case only a mammogram of the remaining breast is required

- No metastases confirmed by 1 of the following methods:

- Bone scan* (required only if alkaline phosphatase is at least 2 times normal
and/or there are symptoms of metastatic disease)

- Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline
phosphatase is at least 2 times normal, unless the elevation is in the bone
fraction)

- Chest x-ray NOTE: *Confirmatory x-ray, CT scan, or MRI required if the bone scan
results are questionable

- No locally recurrent disease

- No prior or concurrent carcinoma in situ of the contralateral breast treated with
partial mastectomy and/or hormonal therapy

- Patients with prior or concurrent carcinoma in situ of the ipsilateral breast
are eligible provided the tumor was completely excised AND they have not
received prior hormonal therapy

- Hormone receptor status:

- Estrogen receptor- and/or progesterone receptor-positive by immunohistochemistry
or tumor receptor content ≥ 10 fmol/mg protein

PATIENT CHARACTERISTICS:

Age

- Postmenopausal

Sex

- Female

Menopausal status

- Postmenopausal prior to chemotherapy, defined as 1 of the following:

- Over 60 years of age

- Age 45-59 with spontaneous cessation of menses for more than 1 year prior to
study entry

- Age 45-59 with menses ceasing (secondary to hysterectomy or spontaneously)
within the past year AND a follicle-stimulating hormone (FSH) level prior to
study entry in the postmenopausal range*

- Age 45-59, previously on hormone replacement therapy (HRT) and have discontinued
HRT upon diagnosis of this malignancy AND has an FSH level prior to study entry
in the postmenopausal range*

- Has undergone bilateral oophorectomy NOTE: *By institutional standards OR > 34.4
IU/L if institutional range is not available)

Performance status

- ECOG 0-2

Life expectancy

- At least 5 years

Hematopoietic

- WBC at least 3,000/mm^3 OR

- Granulocyte count at least 1,500/mm^3 AND

- Platelet count at least 100,000/mm^3

Hepatic

- See Disease Characteristics

- AST and/or ALT less than 2 times upper limit of normal (ULN)*

- Alkaline phosphatase less than 2 times ULN* NOTE: *Unless imaging examinations have
ruled out metastatic disease

Renal

- Not specified

Other

- Able to swallow study medication and have adequate unassisted oral intake in order to
maintain reasonable nutrition status

- No other non-breast malignancy within the past 5 years except adequately treated
nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other
curatively treated solid tumors with no evidence of disease for at least 5 years

- No other concurrent medical or psychiatric condition that would preclude study
participation and/or interfere with results

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior and concurrent trastuzumab (Herceptin®) allowed

Chemotherapy

- See Disease Characteristics

- At least 3 weeks but no more than 3 months since prior chemotherapy

- Prior adjuvant chemotherapy allowed

Endocrine therapy

- See Disease Characteristics

- No prior aromatase inhibitor

- No prior tamoxifen or other selective estrogen receptor modulators (SERMs) except
raloxifene

- At least 3 weeks since prior raloxifene

- At least 3 weeks since prior and no concurrent over-the-counter products or
supplements considered to have an estrogenic effect, including any of the following:

- Ginseng

- Ginkgo biloba

- Black cohosh

- Dong quai

- Fortified soy supplements (e.g., phytoestrogen preparations)

- At least 3 weeks since other prior hormonal therapy or steroids considered to have an
estrogenic effect

- No concurrent estrogens, progesterones, androgens, or SERMs

- Concurrent intermittent vaginal estrogens (e.g., vagifem, estrogen vaginal
cream, testosterone, estradiol vaginal gel, or Estring) allowed if other local
measures for intractable vaginal atrophy are insufficient

- No other concurrent therapy that would have an estrogenic effect, including endocrine
therapy, hormonal therapy, or steroid therapy

Radiotherapy

- See Disease Characteristics

- Prior adjuvant radiotherapy allowed

- Concurrent radiotherapy allowed

Surgery

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Event-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:

MA27

NCT ID:

NCT00066573

Start Date:

June 2003

Completion Date:

March 2011

Related Keywords:

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

Name

Location