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

Alternate Title

Suppression of Ovarian Function Plus Either Tamoxifen or Exemestane Compared With Tamoxifen Alone 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-2402 BIG-2-02, CALGB-IBCSG-2402, CAN-NCIC-IBCSG-2402, NCCTG-IBCSG-2402, NSABP-IBCSG-2402, SWOG-IBCSG-2402, NABCI-IBCSG-2402, UCLA-0403024-01, EU-20334, IBCSG-24-02, NCT00066690, EUDRACT-2004-000166-13

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. 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.
2. Compare the disease-free and overall survival of patients treated with these regimens.
3. Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
4. Compare the incidence of second (nonbreast) malignancies in patients treated with these regimens.
5. Compare the sites of first treatment failure 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
      • 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 sentinal 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

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

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

Expected Enrollment

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

Outcomes

Disease-free survival at 5 years

Overall survival at 5 years
Systemic disease-free survival at 5 years
Quality of life as measured by presence of menopausal symptoms (e.g., hot flushes) and/or loss of sexual interest at 0, 6, 12,18, 24, 36, 48, 60, and 72 months from randomization

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 intented 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.

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

Prudence Francis, MD, Protocol chair		Ph: 61-39-656-1701 Email: Prue.Francis@petermac.org

Breast International Group

Prudence Francis, MD, Protocol chair		Ph: 61-39-656-1701 Email: Prue.Francis@petermac.org

Cancer and Leukemia Group B

Gini Fleming, MD, Protocol chair		Ph: 773-702-6712; 888-824-0200 Email: gfleming@medicine.bsd.uchicago.edu

NCIC-Clinical Trials Group

Barbara Walley, MD, FRCPC, Protocol chair		Ph: 403-521-3688 Email: bwalley@cancerboard.ab.ca

North Central Cancer Treatment Group

James Ingle, MD, Protocol chair		Ph: 507-284-8432 Email: ingle.james@mayo.edu

National Surgical Adjuvant Breast and Bowel Project

Charles Geyer, FACP, MD, Protocol chair		Ph: 412-359-8353; 866-680-0004

Southwest Oncology Group

Silvana Martino, DO, Protocol chair		Ph: 310-582-7900 Email: martinos@jwci.org

U.S.A.
Alabama
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
California
	Arroyo Grande
	Arroyo Grande Community Hospital
		David Palchak, MD	Ph:  805-773-7127
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Castro Valley
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Concord
	Cancer Care Center at John Muir Health - Concord Campus
		Clinical Trials Office - Cancer Care Center at John Muir Health - Concord Campus	Ph:  925-674-2580
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Fresno
	California Cancer Center - Woodward Park Office
		Dina Ibrahim	Ph:  559-451-3647
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Greenbrae
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-1591
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-1591
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Scripps Cancer Center - San Diego
		Joan Kroener, MD	Ph:  858-554-8629
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5814
	Oakland
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Palo Alto
	Palo Alto Medical Foundation
		David Leibowitz	Ph:  650-321-4121
	Pleasanton
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Rancho Mirage
	Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
		Luke Dreisbach	Ph:  760-674-3600
	Redding
	Mercy Regional Cancer Center at Mercy Medical Center
		Clinical Trials Office - Mercy Regional Cancer Center	Ph:  530-225-7471
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Mercy General Hospital
		Mansoor Javeed	Ph:  916-453-4453
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Salinas
	Salinas Valley Memorial Hospital
		Shehzad Aziz, MD	Ph:  831-755-1701
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-5888
	Veterans Affairs Medical Center - San Diego
		Barbara Parker	Ph:  858-552-8585
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-1591
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Francisco General Hospital Medical Center
		Hope Rugo, MD	Ph:  415-353-7428
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Denver Health Medical Center
		Anthony Elias, MD	Ph:  720-848-1622
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Veterans Affairs Medical Center - Denver
		Anthony Elias, MD	Ph:  720-848-1622
	Edwards
	Shaw Regional Cancer Center
		Anthony Elias, MD	Ph:  720-848-1622
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Fort Collins
	Front Range Cancer Specialists
		Robert Marschke, Jr.	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
Connecticut
	Hartford
	Helen and Harry Gray Cancer Center at Hartford Hospital
		Clinical Trials Office - Helen and Harry Gray Cancer Center	Ph:  860-545-5363
	Norwalk
	Norwalk Hospital
		Richard Frank, MD	Ph:  203-845-2132
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Kandhasamy Jagathabal, MD	Ph:  860-886-8362
	Stamford
	Carl and Dorothy Bennett Cancer Center at Stamford Hospital
		Clinical Trials Office - Carl and Dorothy Bennett Cancer Center	Ph:  203-323-8944
	Torrington
	Connecticut Oncology & Hematology - Torrington
		Michael Magnifico, MD	Ph:  860-482-5384
Delaware
	Dover