Sorafenib and Letrozole, Anastrozole, or Exemestane in Treating Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Metastatic Breast Cancer
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.
|Breast Cancer||Drug: anastrozole Drug: exemestane Drug: letrozole Drug: sorafenib tosylate Other: placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Phase II Randomized Study of Sorafenib Compared to Placebo When Administered in Combination With Aromatase Inhibitors for Postmenopausal Women With Metastatic Breast Cancer|
- Progression-free Survival [ Time Frame: 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.
- Overall Survival [ Time Frame: Time from randomization to death (up to 5 years) ]Survival time was defined as the time from randomization to death due to any cause.
- Time to Treatment Failure [ Time Frame: 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.
- Objective Tumor Response Rate [ Time Frame: 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.
- Duration of Response [ Time Frame: 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.
- Adverse Event [ Time Frame: 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.
|Study Start Date:||December 2007|
|Study Completion Date:||April 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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.
given orallyDrug: exemestane
given orallyDrug: letrozole
given orallyDrug: sorafenib tosylate
Active Comparator: Arm II
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.
given orallyDrug: exemestane
given orallyDrug: letrozole
given orallyOther: placebo
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00573755
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 55259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Vivek Roy, MD||Mayo Clinic|
|Principal Investigator:||Donald W Northfelt, M.D.||Mayo Clinic|
|Principal Investigator:||Timothy J Hobday, M.D.||Mayo Clinic|