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 and Either Tamoxifen or Exemestane With or Without Chemotherapy in Treating Premenopausal Women With Resected Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed Premenopausal NCI IBCSG-26-02 BIG-4-02, NABCI-IBCSG-26-02, EU-20401, IBCSG-26-02, NCT00066807, EUDRACT-2005-002626-59

Special Category: CTSU trial

Objectives

1. Compare ovarian function suppression and tamoxifen or exemestane with vs without adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast cancer.
2. Compare the disease-free and overall survival of patients treated with these regimens.
3. Compare sites of first treatment failure in patients treated with these regimens.
4. Compare the incidence of second nonbreast malignancies in patients treated with these regimens.
5. Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer confined to the breast and axillary nodes
  • No distant metastatic disease
  • Tumor detected in the internal mammary chain by sentinel node procedure allowed



• Must have undergone 1 of the following procedures for primary breast cancer within the past 12 weeks and have no known clinical residual locoregional disease:
  • Total mastectomy with or without adjuvant radiotherapy
  • Breast-conserving surgery (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins clear* of invasive cancer and ductal carcinoma in situ) followed by 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]




• Prior axillary lymph node dissection or negative axillary sentinel node biopsy required
  • Patients with microscopically positive axillary sentinel nodes allowed provided they were evaluated on a clinical trial evaluating microscopically positive lymph nodes



• No locally advanced, inoperable breast cancer, including any of the following characteristics:
  • 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 receptor and/or progesterone receptor positive in each tumor
    • At least 10% of tumor cells positive by immunohistochemistry

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior neoadjuvant or adjuvant chemotherapy
  • Neoadjuvant or adjuvant trastuzumab (Herceptin®) allowed

Endocrine therapy

• No prior neoadjuvant or adjuvant endocrine therapy after breast cancer diagnosis
• No prior tamoxifen or other selective estrogen-receptor modulator (e.g., raloxifene) within 1 year before the breast cancer diagnosis
• No other concurrent oral or transdermal hormonal therapy, including any of the following:
  • Estrogen
  • Progesterone
  • Androgens
  • Aromatase inhibitors
  • Hormone replacement therapy
  • Oral or other hormonal contraceptives, including implant and depot injections
  • Raloxifene or other selective estrogen-receptor modulators

Radiotherapy

• See Disease Characteristics
• No prior ovarian irradiation

Surgery

• See Disease Characteristics
• No prior bilateral oophorectomy

Other

• No other prior neoadjuvant therapy
• No other concurrent investigational agents
• No concurrent bisphosphonates unless bone density has been documented at least 1.5 standard deviations below the young adult normal mean or the patient is participating in a randomized clinical trial setting testing bisphosphonates in the adjuvant breast cancer setting

Patient Characteristics:

Age

• Premenopausal

Sex

• Female

Menopausal status

• Premenopausal
  • Estradiol in the premenopausal range after surgery

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 prior deep venous thrombosis and/or embolism unless patient is medically suitable
• No systemic cardiovascular disease that would preclude prolonged follow-up

Pulmonary

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

Other

• Not pregnant or nursing
• Fertile patients must use effective nonhormonal contraception
• No other prior or concurrent invasive malignancy except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ without invasion, contralateral or ipsilateral carcinoma in situ of the breast
• No prior or concurrent nonbreast invasive malignancy within the past 5 years that is nonrecurrent 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 other nonmalignant systemic disease that would preclude prolonged follow-up
• No history of noncompliance with medical regimens
• No psychiatric, addictive, or other disorder that would preclude study compliance or giving informed consent

Expected Enrollment

A total of 1,750 patients will be accrued for this study within 7 years.

Outcomes

Relapse (i.e., local, regional, or distant)
Contralateral breast cancer
Second (nonbreast) primary tumor
Death

Overall survival

Outline

This is a randomized, multicenter study. Patients are stratified according to participating center, number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more), method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation), chemotherapy if randomized to arm II (not containing vs containing an anthracycline or taxane), and endocrine agent (tamoxifen vs exemestane vs selected by subsequent randomization in the TEXT trial). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive ovarian function suppression comprising triptorelin intramuscularly on day 1 every 28 days for 5 years, oophorectomy, or ovarian irradiation. Beginning when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane once daily for 5 years in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive ovarian function suppression as in arm I and concurrent chemotherapy for at least 2 months (if an anthracycline is included) or at least 4 months (if no anthracycline is included). Beginning after the completion of chemotherapy or when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane as in arm I.

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

Rosalba Torrisi, MD, Protocol chair		Ph: 39-02-5748-9482 Email: rosalba.torrisi@ieo.it

Breast International Group

Rosalba Torrisi, MD, Protocol chair		Ph: 39-02-5748-9482 Email: rosalba.torrisi@ieo.it

Related Information

Web site for additional information

Registry Information
Official Title		A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women with Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy
Trial Start Date		2003-08-04
Registered in ClinicalTrials.gov		NCT00066807
Date Submitted to PDQ		2003-07-02
Information Last Verified		2007-04-05