Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Drug: paclitaxel
Drug: sorafenib tosylate

Registration Number: NCT00622466

Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary: 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. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with paclitaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving sorafenib together with paclitaxel and to how well it works in treating patients with metastatic breast cancer.

Detailed Description: OBJECTIVES:

Primary

* To evaluate the efficacy of sorafenib tosylate and paclitaxel by measuring tumor response, as defined by RECIST criteria, in patients with metastatic, HER2-negative breast cancer.

Secondary

* To evaluate time to disease progression in patients treated with this regimen.

* To evaluate six-month progression-free survival of patients treated with this regimen.

* To evaluate time to treatment failure in patients treated with this regimen.

* To evaluate clinical benefit rate (tumor response and stable disease) at 24 weeks in patients treated with this regimen.

* To evaluate duration of response in patients treated with this regimen.

* To evaluate the tolerability of this regimen in these patients.

* To examine the relationship of gene expression and tissue/serum protein markers, where available, related to response to therapy focusing on growth factor receptor pathways.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorfenib + Paclitaxel	sorafenib tosylate	Oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15
Sorfenib + Paclitaxel	paclitaxel	Oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15

Primary Outcome Measures

Name	Time	Method
Time to Tumor Progression	Time from first treatment to disease progression or death (up to 36 months)	Progression-free survival was defined as the time of treatment to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment. Tenth month of progression-free rate of sorafenib and paclitaxel will be compared agains the null progression free rate of 32% using normal approximation test.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate (Tumor Response and Stable Disease) at 24 Weeks	24 weeks	Number of patients with either complete response (CR) or partial response (PR) as defined in Response Evaluation Criteria in Solid Tumors (for patients with measurable disease). Complete Response: Disappearance of all target lesions, disappearance of all non-target lesions for at least 4 weeks. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.
Tumor Response Rate	Up to 36 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT and MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. The confirmed response rate was estimated by the number of confirmed responses divided by the total number of participants randomized.
Time to Treatment Failure	Up to 36 months	Number of patients experiencing treatment failure.
Tolerability of Sorafenib/Paclitaxel Regimen	Up to 36 months	Number of patients without experiencing treatment-related adverse events.
Six-month Progression-free Survival	6 months	The proportion of patients with progression-free survival at 6 months. Progression-free is measured from Day-1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Sole Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new leasions.
Duration of Response	Up to 36 months	Number weeks until disease progression measured from Day-1 of study drug administration to disease progression.
Determine the Relationship of Gene Expression and Tissue/Serum Protein Markers, Where Available, Related to Response to Therapy Focusing on Growth Factor Receptor Pathways.	Up to 36 months	Median values taken for all assays at baseline and relationship to response vs. no response will be made to identify predictive markers using methods to detect differential expression between two groups samples, including variants of the two-sample t-test, analysis of variance, F-test, and the Wilcoxon rank-sum test.