Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer
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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. 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Estrogen Receptor-positive Breast Cancer Progesterone Receptor-positive Breast Cancer Stage IA Breast Cancer Stage IB Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer |
Drug: tamoxifen citrate Drug: triptorelin Drug: exemestane Procedure: quality-of-life assessment Other: laboratory biomarker analysis |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Disease-free survival (DFS) [ Time Frame: From randomization to local, regional or distant relapse, contralateral breast cancer, appearance of a second (non-breast) primary tumor, or death from any cause, whichever occurs first, assessed up to 6 years ] [ Designated as safety issue: No ]Using two-sided stratified logrank tests to determine if the treatment groups are different, with an alpha level of 0.05. Kaplan-Meier estimates of the DFS distributions will be calculated for each of the two arms. Cox proportional hazards regression models will be used to investigate whether the treatment comparison is modified by adjustments for various covariates.
- Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 6 years ] [ Designated as safety issue: No ]
- Breast cancer-free interval [ Time Frame: From randomization to the earliest time of invasive breast recurrence or a new invasive breast cancer in the contralateral breast, assessed up to 6 years ] [ Designated as safety issue: No ]
- Distant recurrence-free interval [ Time Frame: From randomization to the earliest time of distant recurrence, assessed up to 6 years ] [ Designated as safety issue: No ]
- Change in quality of life [ Time Frame: At baseline 6, 12, 18, 24, 36, 48, 60, and 72 months ] [ Designated as safety issue: No ]
- Sites of first treatment failure [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
- Late side effects of early menopause [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
- Incidence of second (non-breast) malignancies [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
- Causes of death without recurrence [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 2639 |
| Study Start Date: | August 2003 |
| Estimated Primary Completion Date: | December 2031 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I (triptorelin, tamoxifen)
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.
|
Drug: tamoxifen citrate
Given orally
Other Names:
Drug: triptorelin
Given IM
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Arm II (triptorelin, exemestane)
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.
|
Drug: triptorelin
Given IM
Other Names:
Drug: exemestane
Given orally
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
OBJECTIVES:
I. 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.
II. Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
III. Compare the sites of first treatment failure in patients treated with these regimens.
IV. Compare the incidence of second (non-breast) malignancies in patients treated with these regimens.
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.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
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
- Female
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
- No systemic hepatic disease that would preclude prolonged follow-up
- No systemic renal disease that would preclude prolonged follow-up
- 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
- No systemic pulmonary disease that would preclude prolonged follow-up
- 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, non-breast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other non recurrent invasive non-breast 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 or concurrent neoadjuvant or adjuvant trastuzumab allowed
- No prior neoadjuvant or adjuvant chemotherapy
- 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)
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 prior ovarian radiotherapy
- No other concurrent investigational agents
- No prior bilateral oophorectomy
Contacts and Locations
Show 245 Study Locations| Principal Investigator: | Barbara Walley | International Breast Cancer Study Group |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00066703 History of Changes |
| Other Study ID Numbers: | NCI-2009-01087, IBCSG 25-02, CDR0000316458, N02CM62212 |
| Study First Received: | August 6, 2003 |
| Last Updated: | May 15, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Federal Government |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Hormones Tamoxifen Triptorelin Exemestane Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents, Hormonal Antineoplastic Agents |
Therapeutic Uses Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Hormone Antagonists Bone Density Conservation Agents Estrogen Antagonists Aromatase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Luteolytic Agents Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents |
ClinicalTrials.gov processed this record on May 16, 2013