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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 HospitalBethesda, Maryland  20814
Roswell Park Cancer InstituteBuffalo, New York  14263
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
CCOP - WichitaWichita, Kansas  67214-3882
CCOP - Atlanta RegionalAtlanta, Georgia  30342-1701
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Dwight David Eisenhower Army Medical CenterFort Gordon, Georgia  30905-5650
Monmouth Medical CenterLong Branch, New Jersey  07740-6395
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Northside Hospital Cancer CenterAtlanta, Georgia  30342-1611
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
St. Vincent's Comprehensive Cancer Center - ManhattanNew York, New York  10011
Chester County HospitalWest Chester, Pennsylvania  19380
Batte Cancer Center at Northeast Medical CenterConcord, North Carolina  28025
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Elkhart General HospitalElkhart, Indiana  46515
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Salinas Valley Memorial HospitalSalinas, California  93901
Kaiser Permanente Medical Office -Vandever Medical OfficeSan Diego, California  92120
John Muir/Mt. Diablo Comprehensive Cancer CenterWalnut Creek, California  94598
Poudre Valley HospitalFort Collins, Colorado  80524
Saint Joseph's Hospital of AtlantaAtlanta, Georgia  30342-1701
Piedmont HospitalAtlanta, Georgia  30309
WellStar Cobb HospitalAustell, Georgia  30106
Charles B. Eberhart Cancer Center at DeKalb Medical CenterDecatur, Georgia  30033
Gwinnett Medical CenterLawrenceville, Georgia  30045
Kennestone Cancer Center at Wellstar Kennestone HospitalMarietta, Georgia  30060
Southern Regional Medical CenterRiverdale, Georgia  30274-2600
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Upper Michigan Cancer Center at Marquette General HospitalMarquette, Michigan  49855
Community Cancer Center of MonroeMonroe, Michigan  48162
Kingsbury Center for Cancer Care at Cheshire Medical CenterKeene, New Hampshire  03431
Wood County Oncology CenterBowling Green, Ohio  43402
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
Fulton County Health CenterWauseon, Ohio  43567
St. Mary Regional Cancer CenterLanghorne, Pennsylvania  19047
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Eastern Connecticut Hematology and Oncology AssociatesNorwich, Connecticut  06360
Carl and Dorothy Bennett Cancer Center at Stamford HospitalStamford, Connecticut  06904
Harbin Clinic Cancer Center - Medical OncologyRome, Georgia  30165
McFarland Clinic, PCAmes, Iowa  50010
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Haematology-Oncology Associates of Ohio and Michigan, PCLambertville, Michigan  48144
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Hematology and Oncology Associates of Northeastern PennsylvaniaScranton, Pennsylvania  18510
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311
Vince Lombardi Cancer Clinic - MarinetteMarinette, Wisconsin  54143
Community HospitalMunster, Indiana  46321
Aurora Sinai Medical CenterMilwaukee, Wisconsin  53201-0342
Lowell General HospitalLowell, Massachusetts  01854
Rutherford HospitalRutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Dana-Farber/Brigham and Women's Cancer CenterBoston, Massachusetts  02115
Glendale Memorial Hospital Comprehensive Cancer CenterGlendale, California  91204
MBCCOP - Meharry Medical College - NashvilleNashville, Tennessee  37208-3599
Providence Cancer CenterAnchorage, Alaska  99508
Cancer Center at Phoenixville HospitalPhoenixville, Pennsylvania  19460
Center for Cancer Care at OSF Saint Anthony Medical CenterRockford, Illinois  61108
Mercy General HospitalSacramento, California  95819
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer CareConcord, New Hampshire  03301
Center for Cancer Care at Exeter HospitalExeter, New Hampshire  03833
New Hampshire Oncology - Hematology, PA - HooksettHooksett, New Hampshire  03106
AnMed Cancer CenterAnderson, South Carolina  29621
NSMC Cancer Center - PeabodyPeabody, Massachusetts  01960
Nashville Oncology Associates, PCNashville, Tennessee  37203
Cancer Care Center at John Muir Health - Concord CampusConcord, California  94524-4110
Renown Institute for Cancer at Renown Regional Medical CenterReno, Nevada  89502
Aurora Women's Pavilion of West Allis Memorial HospitalWest Allis, Wisconsin  53227
Bendheim Cancer Center at Greenwich HospitalGreenwich, Connecticut  06830
Norwalk HospitalNorwalk, Connecticut  06856
Community Regional Cancer Care at Community Hospital NorthIndianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital EastIndianapolis, Indiana  46219
Erlanger Cancer Center at Erlanger Hospital - BaronessChattanooga, Tennessee  37403
Vince Lombardi Cancer Clinic - OshkoshOshkosh, Wisconsin  54904