Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Premenopausal NCI IBCSG-25-02 BIG-3-02, NABCI-IBCSG-25-02, EU-20347, NCT00066703, EUDRACT-2004-000168-28

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Compare the disease-free and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with triptorelin and exemestane vs triptorelin and tamoxifen.
2. Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
3. Compare the sites of first treatment failure in patients treated with these regimens.
4. Compare the incidence of second (non-breast) malignancies in patients treated with these regimens.

Entry 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
    • Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins negative* for invasive disease and ductal carcinoma in situ) with planned radiotherapy

   [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 by sentinel node procedure and is not enlarged is allowed



• Axillary lymph node dissection or a negative axillary sentinel node biopsy required
  • Patients with negative or microscopically positive axillary sentinel nodes are eligible
  • Positive sentinel nodes must have either 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)



• Bilateral synchronous invasive breast cancer allowed if disease meets all other eligibility criteria



• No prior ipsilateral or contralateral invasive breast cancer



• Hormone receptor status:
  • Estrogen and/or progesterone receptor positive
    • At least 10% of the tumor cells positive by immunohistochemistry
    • If > 1 breast tumor, each tumor must be hormone receptor positive

Prior/Concurrent Therapy:

Biologic therapy

• Prior or concurrent neoadjuvant or adjuvant trastuzumab allowed

Chemotherapy

• No prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

• No prior tamoxifen, other selective estrogen-receptor modulators (SERMs) (e.g., raloxifene), or hormone replacement therapy for more than 1 year before breast cancer diagnosis
• No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
• No concurrent oral or transdermal hormonal therapy
• No other concurrent estrogen, progesterone, or androgens
• No other concurrent aromatase inhibitors
• No concurrent oral or other hormonal contraceptives (i.e., implants or depot injections)

Radiotherapy

• See Disease Characteristics
• No prior ovarian radiotherapy

Surgery

• See Disease Characteristics
• No prior bilateral oophorectomy

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 agents

Patient Characteristics:

Age

• Premenopausal

Sex

• Female

Menopausal status

• Premenopausal
  • Estradiol in the premenopausal range after prior surgery OR meets the following criteria:
    • Menstruating regularly for the past 6 months
    • Has not used any form of hormonal treatment (including hormonal contraception) within the past 6 months

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 other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other nonrecurrent invasive nonbreast malignancy, including any of 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

Expected Enrollment

A total of 2,639 patients will be accrued for this study.

Outcomes

Disease-free survival

Overall survival
Systemic disease-free survival
Quality of life
Sites of first recurrence
Late side effects of early menopause
Causes of death without recurrence
Incidence of second (nonbreast) malignancies

Outline

This is a randomized, multicenter study. Patients are stratified according to participating center, concurrent adjuvant chemotherapy (yes vs no), and number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive triptorelin intramuscularly on day 1 every 28 days. Patients in the adjuvant chemotherapy stratum receive chemotherapy concurrently with triptorelin for at least 2 months (if anthracycline is included) or at least 4 months (if no anthracycline is included). Beginning after the completion of chemotherapy or approximately 6-8 weeks after the initiation of triptorelin, patients receive oral tamoxifen daily.



• Arm II: Patients receive triptorelin as in arm I. Beginning after the completion of adjuvant chemotherapy or approximately 6-8 weeks after the initiation of triptorelin, patients also receive oral exemestane daily.

In both arms, 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 annually for 3 years.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.

Trial Contact Information

Trial Lead Organizations

International Breast Cancer Study Group

Olivia Pagani, MD, Protocol chair		Ph: 41-91-811-3395

Breast International Group

Olivia Pagani, MD, Protocol chair		Ph: 41-91-811-3395

U.S.A.
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Sacramento
	Mercy General Hospital
		Mansoor Javeed	Ph:  916-453-4453
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	Whittier
	Ruby L. Golleher Cancer Program at Presbyterian Intercommunity Hospital
		Jack Freimann, MD	Ph:  562-945-6770
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
Florida
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Georgia
	Gainesville
	Northeast Georgia Medical Center
		Richard LoCicero, MD	Ph:  770-297-5700
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		Theodore Walters, MD	Ph:  208-381-2711
	Coeur d'Alene
	Kootenai Cancer Center - Coeur d'Alene
		Clinical Trials Office - North Idaho Cancer Center	Ph:  208-666-3764
Illinois
	Evanston
	Evanston Northwestern Healthcare - Evanston Hospital
		Clinical Trials Office - Evanston Northwestern Healthcare - Evanston Hospital	Ph:  847-570-1381
Indiana
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830
Iowa
	Sioux City
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
Kansas
	Topeka
	Cotton-O'Neil Cancer Center
		Clinical Trials Office - Cotton-O'Neil Cancer Center	Ph:  785-270-4963
Maryland
	Baltimore
	Greenebaum Cancer Center at University of Maryland Medical Center
		Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center	Ph:  800-888-8823
	Bethesda
	Suburban Hospital
		Carolyn Hendricks, MD	Ph:  301-897-1503
	Frederick
	Frederick Memorial Hospital Regional Cancer Therapy Center
		Brian O'Connor, MD	Ph:  301-662-8477
Massachusetts
	Boston
	Beth Israel Deaconess Medical Center
		Clinical Trials Office - Beth Israel Deaconess Medical Center	Ph:  617-667-9925
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Harold J. Burstein, MD, PhD	Ph:  617-632-3800
	Massachusetts General Hospital
		Clinical Trials Office - Massachusetts General Hospital	Ph:  877-726-5130
	Concord
	Bethke Cancer Center at Emerson Hospital
		Clinical Trials Office - Bethke Cancer Center at Emerson Hospital	Ph:  978-287-3460
	Lowell
	Lowell General Hospital
		Harold J. Burstein, MD, PhD	Ph:  617-632-3800
	Peabody
	NSMC Cancer Center - Peabody
		Karen Krag, MD	Ph:  978-977-3434
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Nebraska
	Kearney
	Good Samaritan Cancer Center at Good Samaritan Hospital
		Clinical Trials Office - Good Samaritan Cancer Center at Good Samaritan Hospital	Ph:  308-865-7963
New Jersey
	Marlton
	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
		Clinical Trials Office - Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Ph:  888-847-8823
New York
	Bronx
	Albert Einstein Cancer Center at Albert Einstein College of Medicine
		Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine	Ph:  718-904-2730
			Email: aecc@aecom.yu.edu
	Our Lady of Mercy Medical Center Comprehensive Cancer Center
		Peter Wiernik, MD	Ph:  718-304-7200
	New York
	NYU Cancer Institute at New York University Medical Center
		Amy Tiersten, MD	Ph:  212-731-5349
North Carolina
	Asheboro
	Randolph Hospital
		Clinical Trails Office - Randolph Hospital	Ph:  336-832-0821
	Asheville
	Mission Hospitals - Memorial Campus
		Clinical Trials Office - Mission Hospitals - Memorial Campus	Ph:  828-213-4150
	Greensboro
	Moses Cone Regional Cancer Center at Wesley Long Community Hospital
		Clinical Trials Office - Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Ph:  336-621-8374
	Kinston
	Kinston Medical Specialists
		Peter Watson, MD	Ph:  252-559-2200ext.201
	Reidsville
	Annie Penn Cancer Center
		Clinical Trials Office - Annie Penn Cancer Center	Ph:  336-621-8374
North Dakota
	Bismarck
	Medcenter One Hospital Cancer Care Center
		Edward Wos, DO	Ph:  701-323-5741
Ohio
	Canton
	Aultman Cancer Center at Aultman Hospital
		Clinical Trials Office - Aultman Cancer Center at Aultman Hospital	Ph:  330-363-6891
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Clinical Trials Office - Geisinger Cancer Institute	Ph:  570-271-5251
South Carolina
	Greenville
	CCOP - Greenville
		Jeffrey Giguere, MD, FACP	Ph:  864-987-7000
Washington
	Bellingham
	St. Joseph Cancer Center
		Saul Rivkin, MD	Ph:  206-386-2441
	Seattle
	Group Health Central Hospital
		Clinical Trials Office - Group Health Central Hospital	Ph:  206-287-2900
	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
		Saul Rivkin, MD	Ph:  206-386-2441
	Spokane
	Cancer Care Northwest - Spokane South
		Clinical Trials Office - Cancer Care Northwest - Spokane South	Ph:  509-228-1083
Wisconsin
	Glendale
	Oncology Alliance, SC - Milwaukee - East
		Clinical Trials Office - Oncology Alliance, SC - Milwaukee - East	Ph:  414-906-4480
	Wausau
	University of Wisconcin Cancer Center at Aspirus Wausau Hospital
		Clinical Trials Office - University of Wisconsin Cancer Center	Ph:  608-262-5223
Australia
New South Wales
	Campbelltown
	Cancer Therapy Centre at Campbelltown Hospital
		Stephen Della-Fiorentina, MD	Ph:  61-24-634-4355
	Coffs Harbour
	Coffs Harbour Health Campus
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Lismore
	Lismore Base Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Liverpool
	Cancer Therapy Centre at Liverpool Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Tamworth
	Tamworth Base Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Taree
	Manning Base Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Tweed Heads
	Tweed Heads Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Waratah
	Newcastle Mater Misericordiae Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Queensland
	Brisbane
	Royal Brisbane and Women's Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
South Australia
	Bedford Park
	Flinders Medical Centre
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Tasmania
	Hobart
	Royal Hobart Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Launceston
	Launceston General Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Victoria
	Box Hill
	Box Hill Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	East Melbourne
	Breast Unit Mercy Private
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Peter MacCallum Cancer Centre
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	East Ringwood
	Maroondah Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Fitzroy
	St. Vincent's Hospital - Melbourne
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Heidelberg
	Austin Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Melbourne
	Alfred Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Western Australia
	Perth
	Royal Perth Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Belgium
	Brussels
	Institut Jules Bordet
		Contact Person	Ph:  32-2-541-3501
	Huy
	Centre Hospitalier Hutois
		Joelle Collignon, MD	Ph:  32-8527-2111
	Leuven
	U.Z. Gasthuisberg
		Patrick Neven, MD, PhD	Ph:  32-1634-4213
			Email: patrick.neven@uz.kuleuven.ac.be
	Liege
	CHU Liege - Domaine Universitaire du Sart Tilman
		Guy Jerusalem, MD, PhD	Ph:  32-4-366-7111
			Email: g.jerusalem@chu.ulg.ac.be
	Verviers
	Centre Hospitalier Peltzer-La Tourelle
		Jean Paul Salmon, MD	Ph:  32-87-212-111
Brazil
Rio Grande do Sul
	Porto Alegre
	Hospital de Clinicas de Porto Alegre
		Carlos Menke, MD, PhD	Ph:  55-51-2101-8232