Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving sorafenib together with fulvestrant may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sorafenib together with fulvestrant works in treating patients with locally advanced or metastatic breast cancer that did not respond to aromatase inhibitor therapy.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment|
- Number of Participants With Progression-free Survival at 4 Months [ Time Frame: 4 months after initiating treatment with sorafenib plus fulvestrant. ] [ Designated as safety issue: No ]Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD).
- Objective Response Rate [ Time Frame: Every 8 weeks (two cycles) while receiving study therapy. ] [ Designated as safety issue: No ]
- Time to Progression [ Time Frame: Start of treatment to time of progression. ] [ Designated as safety issue: No ]
- Progression-free Survival [ Time Frame: Start of treatment to time of progression or death, whichever comes first. ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: 28 to 56 days after discontinuation of study therapy ] [ Designated as safety issue: No ]
- Safety and Tolerability Profile [ Time Frame: Continuous throughout study and 28 to 56 days after discontinuation of study therapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2008|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Fulvestrant/ Sorafenib
Fulvestrant: A loading dose will be administered intramuscularly to all subjects during cycle 1 of treatment as follows:
Sorafenib: Subjects will take Sorafenib 800 mg/day administered as 400 mg bid (twice daily)each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until unacceptable toxicity occurs.
Loading dose for cycle 1: 500 mg intramuscular(IM) on Day 1;250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or until unacceptable toxicity occurs requiring discontinuation of study therapyDrug: sorafenib tosylate
Subjects will take sorafenib 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy
- To investigate the clinical activity of sorafenib tosylate and fulvestrant, as determined by a 4-month progression-free survival rate, in patients with hormone receptor-positive locally advanced or metastatic breast cancer that progressed after prior treatment with an aromatase inhibitor.
- To determine the objective response rate in patients treated with this regimen.
- To determine the median time to progression in patients treated with this regimen.
- To determine the progression-free survival of patients treated with this regimen.
- To determine the overall survival of patients treated with this regimen.
- To establish the safety and tolerability profile of this regimen in these patients.
OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients also receive fulvestrant intramuscularly on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 28-56 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00722072
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|Principal Investigator:||Stephen Chui, MD||OHSU Knight Cancer Institute|