Know Cancer

or
forgot password

A Phase III Trial Evaluating The Role Of Ovarian Function Suppression And The Role Of Exemestane As Adjuvant Therapies For Premenopausal Women With Endocrine Responsive Breast Cancer


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

Thank you

Trial Information

A Phase III Trial Evaluating The Role Of Ovarian Function Suppression And The Role Of Exemestane As Adjuvant Therapies For Premenopausal Women With Endocrine Responsive Breast Cancer


OBJECTIVES:

- Compare ovarian function suppression (by triptorelin, oophorectomy, or ovarian
irradiation) in combination with tamoxifen vs tamoxifen alone; exemestane vs tamoxifen
alone; and exemestane vs ovarian function suppression in patients with
endocrine-responsive breast cancer.

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

- Compare the quality of life, including late side effects of early menopause, of
patients treated with these regimens.

- Compare the incidence of second (nonbreast) malignancies in patients treated with these
regimens.

- Compare the sites of first treatment failure in patients treated with these regimens.

- Compare the causes of death without cancer event

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center, prior adjuvant/neoadjuvant chemotherapy (yes vs no), and number of
positive axillary and/or internal mammary lymph nodes (0 vs 1 or more) and intended initial
method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation)
. Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive oral tamoxifen daily.

- Arm II: Patients receive tamoxifen as in arm I and ovarian function suppression by 1 of
the following treatments:

- Triptorelin intramuscularly once every 28 days

- Surgical oophorectomy

- Ovarian irradiation once daily for 4 or 5 days

- Arm III: Patients receive oral exemestane daily and ovarian function suppression as in
arm II.

Treatment continues for 5 years in the absence of disease progression or unacceptable
toxicity.

Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4
years.

After completion of study therapy, patients are followed periodically.

NOTE: Effective April 30, 2010, enrollment will cease...except for sites outside North
America that are also participating in IBCSG-24-02-SOFT-EST

PROJECTED ACCRUAL: A total of 3,000 patients (1,000 per treatment arm) will be accrued for
this study within 5 years.

NOTE: Effective April 30, 2010, enrollment will cease...except for sites outside North
America that are also participating in IBCSG-24-02-SOFT-EST

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed breast cancer

- Completely resected disease

- No clinically detectable residual loco-regional axillary disease

- Prior surgery for primary breast cancer of 1 of the following types:

- Total mastectomy with or without adjuvant radiotherapy

- Ductal carcinoma in situ at a margin is permitted if a complete
mastectomy has been performed

- Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial
mastectomy with margins clear* of invasive disease and ductal carcinoma in
situ) with radiotherapy

- No more than 12 weeks since prior surgery if no adjuvant chemotherapy

- No more than 8 months since prior adjuvant chemotherapy NOTE: *If all other
margins are clear a positive posterior (deep) margin is permitted, provided the
excision was performed down to the pectoral fascia and all tumor has been
removed OR a positive anterior (superficial; abutting skin) margin is allowed
provided all tumor was removed

- Tumor confined to the breast and axillary nodes

- Tumor detected in internal mammary chain nodes that are not enlarged is allowed

- Prior neoadjuvant therapy allowed provided disease was operable prior to neoadjuvant
therapy

- Axillary lymph node dissection or a negative axillary sentinel node biopsy required

- Patients with microscopically positive axillary sentinel nodes or negative
sentinel nodes do not require further axillary therapy

- Patients with positive sentinel nodes must have axillary dissection or radiation
of axillary nodes

- No distant metastases

- No locally advanced inoperable breast cancer, including any of the following:

- Inflammatory breast cancer

- Supraclavicular node involvement

- Enlarged internal mammary nodes (unless pathologically negative)

- No prior ipsilateral or contralateral invasive breast cancer

- Histologically diagnosed synchronous bilateral invasive breast cancer within the
past 2 months allowed if the bilateral disease meets all other eligibility
criteria

- Hormone receptor status:

- Estrogen and/or progesterone receptor positive

- Each tumor must be hormone receptor positive

PATIENT CHARACTERISTICS:

Age

- Premenopausal

Sex

- Female

Menopausal status

- Premenopausal

- Estradiol in the premenopausal range, unless the patient meets the following
criteria within the past 6 months:

- No chemotherapy

- Menstruating regularly

- No use of hormonal contraception

- No other use of hormonal treatments

- Temporary chemotherapy-induced amenorrhea allowed provided premenopausal status
is confirmed by estradiol level within 8 months of the final dose of
chemotherapy

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- No systemic hepatic disease that would preclude prolonged follow-up

Renal

- No systemic renal disease that would preclude prolonged follow-up

Cardiovascular

- No systemic cardiovascular disease that would preclude prolonged follow-up

- No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is
medically suitable

Pulmonary

- No systemic pulmonary disease that would preclude prolonged follow-up

Other

- Not pregnant or nursing

- Fertile patients must use effective nonhormonal contraception

- No history of noncompliance to medical regimens

- No other nonmalignant systemic disease that would preclude prolonged follow-up

- No prior or concurrent invasive malignancy except adequately treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix or bladder, contralateral
or ipsilateral carcinoma in situ of the breast, or nonbreast invasive malignancy
diagnosed at least 5 years ago without recurrence, including only the following:

- Stage I papillary thyroid cancer

- Stage IA carcinoma of the cervix

- Stage IA or B endometrioid endometrial cancer

- Borderline or stage I ovarian cancer

- No psychiatric, addictive, or other disorder that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior and/or concurrent adjuvant, trastuzumab (herceptin) allowed

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- More than 1 year since prior selective estrogen-receptor modulators (SERMs) before
the breast cancer diagnosis

- No hormone replacement therapy during the year before the breast cancer diagnosis

- No prior endocrine therapy, including adjuvant or neoadjuvant therapy, for more than
8 months after breast cancer diagnosis

- No prior gonadotropin-releasing hormone analogues for breast cancer

- No concurrent oral or transdermal hormonal therapy

- No other concurrent estrogen, progesterone, or androgens

- No other concurrent aromatase inhibitors

- No concurrent hormone replacement therapy

- No concurrent oral or other hormonal contraceptives (i.e., implants or depot
injections)

- No other concurrent SERMs (e.g., raloxifene)

Radiotherapy

- See Disease Characteristics

- No prior ovarian radiotherapy

Surgery

- See Disease Characteristics

- No prior bilateral oophorectomy

- No concurrent oophorectomy unless performed as part of this study

- No patients who have been recommended to undergo oophorectomy within the next 5
years (e.g., BRCA1/2 gene carrier)

Other

- No concurrent bisphosphonates, except in the following cases:

- Bone density is at least 1.5 standard deviations below the young adult normal
mean

- Participation in a randomized clinical study testing bisphosphonates in the
adjuvant breast cancer setting

- No other concurrent investigational agent

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Time Frame:

For first time at a median follow up approximately 5 years

Safety Issue:

No

Principal Investigator

Prudence Francis, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Peter MacCallum Cancer Centre, Australia

Authority:

United States: Federal Government

Study ID:

CDR0000316456

NCT ID:

NCT00066690

Start Date:

August 2003

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IA breast cancer
  • stage IB breast cancer
  • estrogen receptor-positive breast cancer
  • progesterone receptor-positive breast cancer
  • Breast Neoplasms

Name

Location

Suburban Hospital Bethesda, Maryland  20814
Roswell Park Cancer Institute Buffalo, New York  14263
CCOP - Upstate Carolina Spartanburg, South Carolina  29303
CCOP - Wichita Wichita, Kansas  67214-3882
CCOP - Atlanta Regional Atlanta, Georgia  30342-1701
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - Maplewood Maplewood, Minnesota  55109
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PC Sioux Falls, South Dakota  57105
Memorial Hospital of South Bend South Bend, Indiana  46601
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756-0002
Dwight David Eisenhower Army Medical Center Fort Gordon, Georgia  30905-5650
Monmouth Medical Center Long Branch, New Jersey  07740-6395
St. Vincent Mercy Medical Center Toledo, Ohio  43608
Northside Hospital Cancer Center Atlanta, Georgia  30342-1611
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx, New York  10461
Mission Hospitals - Memorial Campus Asheville, North Carolina  28801
Medical University of Ohio Cancer Center Toledo, Ohio  43614
Toledo Hospital Toledo, Ohio  43606
Baylor University Medical Center - Houston Houston, Texas  77030-2399
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital Huntington, West Virginia  25701
St. Vincent's Comprehensive Cancer Center - Manhattan New York, New York  10011
Chester County Hospital West Chester, Pennsylvania  19380
Batte Cancer Center at Northeast Medical Center Concord, North Carolina  28025
Wayne Memorial Hospital, Incorporated Goldsboro, North Carolina  27534
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Boston, Massachusetts  02115
Don Monti Comprehensive Cancer Center at North Shore University Hospital Manhasset, New York  11030
Elkhart General Hospital Elkhart, Indiana  46515
Lakeland Regional Cancer Care Center - St. Joseph St. Joseph, Michigan  49085
Front Range Cancer Specialists Fort Collins, Colorado  80528
Salinas Valley Memorial Hospital Salinas, California  93901
Kaiser Permanente Medical Office -Vandever Medical Office San Diego, California  92120
John Muir/Mt. Diablo Comprehensive Cancer Center Walnut Creek, California  94598
Poudre Valley Hospital Fort Collins, Colorado  80524
Saint Joseph's Hospital of Atlanta Atlanta, Georgia  30342-1701
Piedmont Hospital Atlanta, Georgia  30309
WellStar Cobb Hospital Austell, Georgia  30106
Charles B. Eberhart Cancer Center at DeKalb Medical Center Decatur, Georgia  30033
Gwinnett Medical Center Lawrenceville, Georgia  30045
Kennestone Cancer Center at Wellstar Kennestone Hospital Marietta, Georgia  30060
Southern Regional Medical Center Riverdale, Georgia  30274-2600
Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte, Indiana  46350
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
Upper Michigan Cancer Center at Marquette General Hospital Marquette, Michigan  49855
Community Cancer Center of Monroe Monroe, Michigan  48162
Kingsbury Center for Cancer Care at Cheshire Medical Center Keene, New Hampshire  03431
Wood County Oncology Center Bowling Green, Ohio  43402
Lima Memorial Hospital Lima, Ohio  45804
Northwest Ohio Oncology Center Maumee, Ohio  43537
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
Fulton County Health Center Wauseon, Ohio  43567
St. Mary Regional Cancer Center Langhorne, Pennsylvania  19047
Massachusetts General Hospital Boston, Massachusetts  02114-2617
Missouri Baptist Cancer Center St. Louis, Missouri  63131
Eastern Connecticut Hematology and Oncology Associates Norwich, Connecticut  06360
Carl and Dorothy Bennett Cancer Center at Stamford Hospital Stamford, Connecticut  06904
Harbin Clinic Cancer Center - Medical Oncology Rome, Georgia  30165
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Independence Independence, Kansas  67301
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Lawrence Memorial Hospital Lawrence, Kansas  66044
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville, Michigan  48144
Mercy Memorial Hospital - Monroe Monroe, Michigan  48162
Flower Hospital Cancer Center Sylvania, Ohio  43560
St. Anne Mercy Hospital Toledo, Ohio  43623
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
Hematology and Oncology Associates of Northeastern Pennsylvania Scranton, Pennsylvania  18510
Fredericksburg Oncology, Incorporated Fredericksburg, Virginia  22401
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center Green Bay, Wisconsin  54311
Vince Lombardi Cancer Clinic - Marinette Marinette, Wisconsin  54143
Community Hospital Munster, Indiana  46321
Aurora Sinai Medical Center Milwaukee, Wisconsin  53201-0342
Lowell General Hospital Lowell, Massachusetts  01854
Rutherford Hospital Rutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Dana-Farber/Brigham and Women's Cancer Center Boston, Massachusetts  02115
Glendale Memorial Hospital Comprehensive Cancer Center Glendale, California  91204
MBCCOP - Meharry Medical College - Nashville Nashville, Tennessee  37208-3599
Providence Cancer Center Anchorage, Alaska  99508
Cancer Center at Phoenixville Hospital Phoenixville, Pennsylvania  19460
Center for Cancer Care at OSF Saint Anthony Medical Center Rockford, Illinois  61108
Mercy General Hospital Sacramento, California  95819
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care Concord, New Hampshire  03301
Center for Cancer Care at Exeter Hospital Exeter, New Hampshire  03833
New Hampshire Oncology - Hematology, PA - Hooksett Hooksett, New Hampshire  03106
AnMed Cancer Center Anderson, South Carolina  29621
NSMC Cancer Center - Peabody Peabody, Massachusetts  01960
Nashville Oncology Associates, PC Nashville, Tennessee  37203
Cancer Care Center at John Muir Health - Concord Campus Concord, California  94524-4110
Renown Institute for Cancer at Renown Regional Medical Center Reno, Nevada  89502
Aurora Women's Pavilion of West Allis Memorial Hospital West Allis, Wisconsin  53227
Bendheim Cancer Center at Greenwich Hospital Greenwich, Connecticut  06830
Norwalk Hospital Norwalk, Connecticut  06856
Community Regional Cancer Care at Community Hospital North Indianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital East Indianapolis, Indiana  46219
Erlanger Cancer Center at Erlanger Hospital - Baroness Chattanooga, Tennessee  37403
Vince Lombardi Cancer Clinic - Oshkosh Oshkosh, Wisconsin  54904