A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women With Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy
N/A
N/A
Female
Breast Cancer
Trial Information
A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women With Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy
OBJECTIVES:
- Compare ovarian function suppression and tamoxifen or exemestane with vs without
adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast
cancer.
- Compare the disease-free and overall survival of patients treated with these regimens.
- Compare sites of first treatment failure in patients treated with these regimens.
- Compare the incidence of second nonbreast malignancies in patients treated with these
regimens.
- Compare the quality of life, including late side effects of early menopause, of
patients treated with these regimens.
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.
PROJECTED ACCRUAL: A total of 1,750 patients will be accrued for this study within 7 years.
Inclusion 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
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
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Relapse (i.e., local, regional, or distant)
Outcome Time Frame:
7 years after inclusion of last patient
Safety Issue:
No
Principal Investigator
Rosalba Torrisi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
European Institute of Oncology
Authority:
Australia: Department of Health and Ageing Therapeutic Goods Administration
Study ID:
CDR0000318832
NCT ID:
NCT00066807
Start Date:
August 2003
Completion Date:
Related Keywords:
- Breast Cancer
- stage IIIA breast cancer
- stage I breast cancer
- stage II breast cancer
- Breast Neoplasms
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