Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066573
• Other study ID #: MA27
• Secondary ID: CAN-NCIC-MA27NCC
• Status: Completed
• Phase: Phase 3
• Start date: June 6, 2003
• Est. completion date: January 6, 2012

Study information

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

Clinical Trial Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy, using exemestane or anastrozole, may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole in preventing the recurrence of breast cancer.

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer.

Description:

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.

Other known NCT identifiers

• NCT00438529

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7576
• Est. completion date: January 6, 2012
• Est. primary completion date: November 7, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• anastrozole
Given orally
• exemestane
Given orally

Locations

Country	Name	City	State
Canada	Quinte Healthcare Corporation	Belleville	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cambridge Memorial Hospital	Cambridge	Ontario
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	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	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	Lethbridge Cancer Centre	Lethbridge	Alberta
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 - Hopital Notre-Dame	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Penticton Regional Hospital	Penticton	British Columbia
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	Regional Cancer Program of the Hopital Regional	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	St. Michael's 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

Sponsors (7)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, ETOP IBCSG Partners Foundation, National Cancer Institute (NCI), North Central Cancer Treatment Group, SWOG Cancer Research Network

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastr — View Citation

Moy B, Elliott CR, Chapman J-AW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3059, S144, 2006.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival	Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.	5 years
Secondary	Overall Survival: Percentage of Participants Alive at 5 Years	Overall survival is defined as the time from randomization to the time of death from any cause.	5 years
Secondary	Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence	Time to distant disease-free survival (DDFS) is defined as the time from randomization to the time of documented distant recurrence. Distant recurrence is the cancer coming back in a part of the body away from the breast, such as the bones or liver.	5 years
Secondary	Clinical Fracture Rate: Number of Participants With Bone Fractures.	Clinical fracture at any time, including hip, spine, wrist fractures and other bone fractures.	8 years