Sorafenib and Letrozole, Anastrozole, or Exemestane in Treating Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Metastatic Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00573755
- Lead Sponsor
- Mayo Clinic
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 4
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II placebo Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I sorafenib tosylate Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I anastrozole Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I exemestane Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II anastrozole Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I letrozole Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II exemestane Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II letrozole Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival Time from randomization to disease progression or death (up to 5 years) 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.
- Secondary Outcome Measures
Name Time Method Overall Survival Time from randomization to death (up to 5 years) Survival time was defined as the time from randomization to death due to any cause.
Adverse Event Time from randomization to end of treatment 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.
Objective Tumor Response Rate Up to 5 years 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 to Treatment Failure Time from randomization to treatment failure (up to 5 years) 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.
Duration of Response Up to 5 years 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.
Trial Locations
- Locations (3)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States