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, IBCSG-25-02, 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

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
			Email: menke@hcpa.ufrgs.br
Egypt
	Cairo
	National Cancer Institute of Egypt
		Hussein Khaled, MD	Ph:  20-2-215-1040
			Email: khaled@internetegypt.com
	Mohandeseen
	Cairo Oncology Center
		Contact Person	Ph:  20-2-302-6814
Germany
	Baden-Baden
	Brustzentrum Klinikum Mittelbaden
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Deggendorf
	Klinikum Deggendorf
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Erlangen
	Frauenklinik des Universitaetsklinikum Erlangen
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Frankfurt
	Universitaetsfrauenklinik Frankfurt
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Goettingen
	Universitaets-Frauenklinik Goettingen
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Karlsruhe
	St. Vincentius - Kliniken
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Luebeck
	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Mainz
	Universitatsklinik Mainz
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Mannheim
	Universitaetsfrauenklinik Mannheim
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Mutlangen
	Klinikum Schwaebisch Gmuend Stauferklinik
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Nuremberg
	Klinikum Nuernberg - Klinikum Nord
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Regensburg
	Caritas - Krankenhaus Saint Josef
		B. Westhauser	Ph:  49-941-782-7511
	Rodewisch
	Klinikum Obergoeltzsch Rodewisch
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Rosenheim
	Klinikum Rosenheim
		GEAG Studiensekretariat	Ph:  49-9417-827-511
	Tuttlingen
	Klinikum Landkreis Tuttlingen
		GEAG Studiensekretariat	Ph:  49-9417-827-511
Hungary
	Budapest
	National Institute of Oncology
		Istvan Lang, MD, PhD, DSc	Ph:  36-1-22-48-763
			Email: lang@oncol.hu
India
	Mumbai
	Tata Memorial Hospital
		Vani Parmar	Ph:  91-22-2417-7194
Italy
	Aviano
	Centro di Riferimento Oncologico - Aviano
		Diana Crivellari, MD	Ph:  39-0434-659-024
			Email: dcrivellari@oro.it
	Bergamo
	Ospedali Riuniti di Bergamo
		Carlo Tondini, MD	Ph:  39-03-526-6424
			Email: carlo.tondoni@ospedaliriuniti.bergamo.it
	Bolzano
	Azienda Sanitaria di Bolzano
		Claudio Graiff, MD	Ph:  39-0471-908-572
			Email: claudio.graiff@asbz.it
	Brescia
	Spedali Civili di Brescia
		Edda Simoncini, MD	Ph:  39-030-3995-410
	Carpi
	Ospedale Civile Ramazzini
		Fabrizio Artioli, MD	Ph:  39-059-659-313
			Email: f.artioli@ausl.mo.it
	Milan
	European Institute of Oncology
		Aron Goldhirsch, MD	Ph:  39-02-574-894-39
			Email: aron.goldhirsch@ibcsg.org
	Pavia
	Fondazione Salvatore Maugeri
		Lorenzo Pavesi	Ph:  39-382-592-669
	Prato
	Misericordia e Dolce Hospital
		Angelo Di Leo, MD	Ph:  39-0574-43-4766
			Email: adileo@usl4.toscana.it
	Rimini
	Ospedale Civile Rimini
		Alberto Ravaioli, MD	Ph:  39-541-705-409
			Email: aravaiol@auslrn.net
	Rozzano
	Istituto Clinico Humanitas
		Armando Santoro, MD	Ph:  39-28-224-4080
			Email: armando.santoro@humanitas.it
	Udine
	Policlinico Universitario Udine
		Fabio Puglisi	Ph:  39-4-3255-9304
			Email: fabio.puglisi@med.uniud.it
	Varese
	Ospedale di Circolo e Fondazione Macchi
		Graziella Pinotti	Ph:  39-332-278-558
New Zealand
	Hamilton
	Waikato Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Peru
	Lima
	Instituto Nacional de Enfermedades Neoplasicas
		Henry Gomez Moreno	Ph:  51-1-710-6900
Republic of South Africa
	Johannesburg
	Sandton Oncology Centre
		Daniel Vorobiof, MD	Ph:  27-11-883-0900
			Email: voro@global.co.za
Slovenia
	Ljubljana
	Institute of Oncology - Ljubljana
		Bojana Pajk, MD	Ph:  386-1-5879-535
Sweden
	Gothenburg
	Sahlgrenska University Hospital
		Per Karlsson, MD	Ph:  46-31-342-1000
	Linkoping
	University Hospital of Linkoping
		Barbro Linderholm	Ph:  46-13-222-000
	Skovde
	Skaraborgs Hospital
		Anders Nissborg, MD	Ph:  46-500-431-000
Switzerland
	Basel
	Universitaetsspital-Basel
		Christoph Rochlitz, MD	Ph:  41-61-265-5059
			Email: crochlitz@uhbs.ch
	Bellinzona
	Oncology Institute of Southern Switzerland
		Olivia Pagani, MD	Ph:  41-91-820-9111
			Email: olivia.pagani@ibcsg.org
	Bern
	Inselspital Bern
		Stefan Aebi, MD	Ph:  41-31-632-4114
			Email: stefan.aebi@insel.ch
	Oncocare Sonnenhof-Klinik Engeriedspital
		Katharina Buser, MD	Ph:  41-31-309-9501
			Email: kbuser@sonnenhof.ch
	Chur
	Kantonsspital Graubuenden
		Roger von Moos, MD	Ph:  41-81-256-6644
			Email: roger.vonmoos@ksgr.ch
	Onkologie-Praxis ZeTup Chur
		Hans-Joerg Senn, MD, PhD	Ph:  44-81-257-0130
	Lausanne
	Centre Hospitalier Universitaire Vaudois
		Khalil Zaman	Ph:  41-21-314-0150
	Locarno
	Ospedale "la Carita", Locarno
		Olivia Pagani, MD	Ph:  41-91-811-3111
	Lugano
	Ospedale Civico
		Olivia Pagani, MD	Ph:  41-91-811-3111
	Mendrisio
	Ospedale Beata Vergine
		Olivia Pagani, MD	Ph:  41-91-811-3395
	St. Gallen
	Kantonsspital - St. Gallen
		Beat Thurlimann, MD	Ph:  41-71-494-1888
			Email: beat.thuerlimann@kssg.ch
	Thun
	Regionalspital
		Jean Marc Luthi, MD	Ph:  41-33-226-2626
	Zurich
	UniversitaetsSpital Zuerich
		Stephanie Von Orelli, MD	Ph:  41-44-255-5313
United Kingdom
England
	Cambridge
	Addenbrooke's Hospital
		Clinical Trials and Statistics Unit - Institute of Cancer Research	Ph:  44-1223-245-151
	Peterborough
	Peterborough Hospitals Trust
		Clinical Trials and Statistics Unit - Institute of Cancer Research	Ph:  44-1733-874-510
	South Shields
	South Tyneside District Hospital
		Clinical Trials and Statistics Unit - Institute of Cancer Research	Ph:  44-191-454-8888

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title		A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer
Trial Start Date		2003-08-04
Trial Completion Date		2007-07-30 (estimated)
Registered in ClinicalTrials.gov		NCT00066703
Date Submitted to PDQ		2003-06-27
Information Last Verified		2008-09-09