RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Aromatase inhibition therapy using letrozole, anastrozole, or exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether sorafenib is more effective than a placebo when given together with letrozole, anastrozole, or exemestane in treating metastatic breast cancer. PURPOSE: This randomized phase II trial is studying how well sorafenib works compared with a placebo when given together with letrozole, anastrozole, or exemestane in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive metastatic breast cancer.
OBJECTIVES: Primary * To compare the progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive metastatic breast cancer treated with sorafenib tosylate vs placebo and letrozole, anastrozole, or exemestane. Secondary * To compare the overall survival and time to treatment failure of patients treated with these regimens. * To compare the objective tumor response rate and duration of response in patients treated with these regimens. * To assess the adverse event profile of sorafenib tosylate in combination with aromatase inhibitors in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior aromatase inhibitor therapy (yes vs no) and line of endocrine therapy for metastatic disease (first-line vs second-line). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. * Arm II: Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
4
given orally
given orally
given orally
given orally
given orally
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Progression-free Survival
Progression-free survival was defined as the time from randomization to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment and then never return for any evaluations, the participant was censored for progression 1 day post-randomization.
Time frame: Time from randomization to disease progression or death (up to 5 years)
Overall Survival
Survival time was defined as the time from randomization to death due to any cause.
Time frame: Time from randomization to death (up to 5 years)
Time to Treatment Failure
Time to treatment failure was defined as the time from the date of the randomization to the date at which the patient was removed from treatment due to progression, adverse events, or refusal.
Time frame: Time from randomization to treatment failure (up to 5 years)
Objective Tumor Response Rate
A confirm response was defined as either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluation at least 4 weeks apart. The confirmed response rate was estimated within each treatment group by the number of confirmed responses divided by the total number of participants randomized.
Time frame: Up to 5 years
Duration of Response
Duration of response was defined for all patients who have achieved a confirmed response as the date at which the patient's earliest best objective status was first noted to be either a CR or PR to the earliest date progression was documented.
Time frame: Up to 5 years
Adverse Event
Number of participants that experienced adverse events (grade 3 and above) as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Adverse events were assessed every week during first 6 weeks of therapy, every 4 weeks on months 1 to 6, every 12 weeks on months 7 and beyond and at the end of treatment.
Time frame: Time from randomization to end of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.