| City: |
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La Crosse |
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State:
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WI |
| Zip Code: |
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54601 |
| Conditions: |
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Breast Cancer |
| Purpose: |
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using
letrozole may fight breast cancer by reducing the production of estrogen.
PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in
treating women with breast cancer who have received tamoxifen for at least 5 years.
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| Study summary: |
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OBJECTIVES:
Primary
- Compare the disease-free survival and overall survival of postmenopausal women with
primary breast cancer who have completed at least five years of adjuvant aromatase
inhibitor as initial therapy or after tamoxifen treated with letrozole or placebo.
Secondary
- Compare the incidence of contralateral breast cancer in patients treated with these
regimens.
- Evaluate the long-term clinical and laboratory safety of letrozole, in terms of lipid
profile, cardiovascular morbidity and mortality, incidence of bone fractures, change in
bone density, and common toxic effects, in this patient population.
- Compare the quality of life of patients treated with these regimens. Re-randomization
Primary
- Compare disease-free survival of patients who, after receiving at least 4.5 years of
letrozole, are re-randomized to receive an additional 5 years of letrozole vs placebo.
Secondary
- Determine whether common genetic polymorphisms for genes encoding proteins involved in
pharmacokinetic and/or pharmacodynamic pathways for letrozole contribute to individual
variation in toxicity and efficacy of letrozole therapy.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to receptor status (positive vs unknown), lymph node status
(negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between
last dose of aromatase inhibitor therapy and randomization (< 6 months vs 6 months-2 years),
and duration of prior tamoxifen use (0 years vs < 2 years vs 2-4.5 years vs > 4.5 years).
Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral letrozole once daily.
- Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for
5 years in the absence of disease progression or unacceptable toxicity. Patients in arm
II may then be offered oral letrozole once daily for up to 5 years.
Quality of life is assessed at baseline, at 6 months, and then annually for 4.5 years.
- Double-blind, re-randomization:
Patients who complete ≥ 4.5 years of letrozole (arm I) and who did not experience recurrent
disease or new primary breast cancer, including ductal carcinoma in situ, may participate in
the double-blind, placebo-controlled, re-randomization portion of the study. Patients are
stratified according to lymph node status at enrollment (negative vs positive vs unknown),
prior adjuvant chemotherapy (yes vs no), and interval between last dose of letrozole and
re-randomization (<6 months vs 6 months to 2 years). Common genetic single nucleotide
polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic
pathways for letrozole are analyzed in order to determine if these single nucleotide
polymorphisms contribute to individual variation in toxicity and efficacy of letrozole
therapy.
Quality of life is assessed as during the first randomization.
Patients are followed annually.
PROJECTED ACCRUAL: A total of 4,700 patients will be accrued for this study. |
| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed primary invasive breast carcinoma resected
at time of original diagnosis
- No ductal carcinoma in situ
- Axillary lymph node negative, positive, or unknown
- No evidence of metastases
- No localized or distant breast cancer recurrence
- Not registered on protocol NCCTG-893052, any other IBCSG protocol, or protocol
SWOG-S9623
- Hormone receptor status:
- Estrogen or progesterone receptor positive as defined by tumor receptor content
at least 10 fmol/mg protein or receptor positive by ERICA or PgRICA
- Unknown status allowed if effort to determine status has been made by
immunocytochemistry
- No contralateral breast cancer
PATIENT CHARACTERISTICS:
Age:
- Postmenopausal
Sex:
- Female
Menopausal status:
- Postmenopausal defined by one of the following:
- Age 50 or over at start of adjuvant tamoxifen
- Under age 50 and considered postmenopausal by treating physician at start of
adjuvant tamoxifen
- Under age 50 at start of adjuvant tamoxifen and had bilateral oophorectomy
(surgical or radiation)
- Under age 50 and premenopausal at start of adjuvant tamoxifen, but became
amenorrheic during tamoxifen and remained amenorrheic for at least 1 year
- Considered postmenopausal by physician with LH/FSH levels under the treatment
center's postmenopausal limits
Performance status:
- ECOG 0-2
Life expectancy:
- At least 5 years
Hematopoietic:
- WBC ≥ 3,000/mm^3 OR
- Granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic:
- AST and/or ALT < 2 times upper limit of normal (ULN) (unless imaging examinations
have ruled out metastatic disease)
- Alkaline phosphatase < 2 times ULN (unless imaging examinations have ruled out
metastatic disease)
Renal:
- Not specified
Other:
- No concurrent medical or psychiatric condition that would preclude study
participation
- No other malignancy within the past 5 years except adequately treated superficial
squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
- Able to swallow study drug
- Adequate oral intake
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Prior adjuvant chemotherapy allowed
- No concurrent chemotherapy
Endocrine therapy:
- Completed at least 4.5 but no more than 6 years of adjuvant tamoxifen after resection
- Completed at least 4.5-6 years of adjuvant aromatase inhibitor as initial therapy or
after tamoxifen
- No more than 3 months since prior adjuvant tamoxifen
- No concurrent hormone replacement therapy (e.g., megestrol)
- No concurrent selective estrogen-receptor modulators (e.g., raloxifene or idoxifene)
- Concurrent intermittent vaginal estrogens (e.g., Estring) allowed if other local
measures for intractable vaginal atrophy are insufficient
- No other concurrent aromatase inhibitors
- No more than 2 years since prior aromatase inhibitor therapy (re-randomization)
Radiotherapy:
- Prior radiotherapy allowed
Surgery:
- See Disease Characteristics
Other:
- At least 1 month since prior investigational drugs
- Prior treatment on a clinical trial for breast cancer allowed if permission has been
obtained from the sponsors of the original study for their patient to participate on
MA.17/JMA.17/BIG-97-01
- No prior placebo on core protocol
- No concurrent anticancer therapy
- Concurrent thyroid medication, calcium, vitamin D, and bisphosphonates allowed |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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April 13, 2010 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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