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

ETOP IBCSG Partners Foundation

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: tamoxifen; Drug: exemestane; Drug: triptorelin

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00066703

NABCI IBCSG 25-02

BIG 3-02 (Other Identifier)

IBCSG 25-02 / BIG 3-02

EU-20347

IBCSG 25-02

2004-000168-28 (EudraCT Number)

CDR0000316458 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving triptorelin together with exemestane is more effective than triptorelin and tamoxifen in treating hormone-responsive breast cancer.

PURPOSE: This randomized phase III trial is studying triptorelin and exemestane to see how well they work compared to triptorelin and tamoxifen in treating premenopausal women with hormone-responsive breast cancer.

Full description

OBJECTIVES:

• Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with triptorelin and exemestane vs triptorelin and tamoxifen.
• Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

OUTLINE: This is a randomized, international, multicenter study. Patients are stratified according to planned use of concurrent adjuvant chemotherapy (yes vs no), and number of positive lymph nodes (0 vs 1 or more). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and annually for 3 years.

Enrollment: 2,672 patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,672 participants in 2 patient groups

T+OFS

Active Comparator group

Description:

Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.

Treatment:

Drug: triptorelin

Drug: tamoxifen

E+OFS

Experimental group

Description:

Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.

Treatment:

Drug: triptorelin

Drug: exemestane