RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, 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 vinorelbine may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib when given together with vinorelbine and to see how well they work in treating women with stage IV breast cancer.
OBJECTIVES: Primary * To determine the safety, tolerability, and recommended phase II dose of sorafenib tosylate when administered in combination with vinorelbine ditartrate in women with stage IV adenocarcinoma of the breast. (Phase I) * To evaluate the 4-month progression-free survival rate in patients treated with this regimen at the maximum tolerated dose. (Phase II) Secondary * To determine time to treatment failure in these patients. * To determine the response rate in these patients. * To determine the overall survival and progression-free survival of these patients. * To evaluate the toxicity profile of this regimen. OUTLINE: This is a phase I, dose-escalation study of sorafenib tosylate followed by a phase II study. Patients receive oral sorafenib tosylate on days 1-28 and vinorelbine ditartrate IV on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Dose level 1 = 200 mg by mouth two times a day on days 1-28 of a 28 day cycle. Dose level 2 = 200 mg by mouth two times a day on days 1-28 of a 28 day cycle. Dose level 3 = 200 mg by mouth in the am and 400 mg by mouth in the pm on days 1-28 of a 28 day cycle. Dose level 4 = 400 mg by mouth two times a day on days 1-28 of a 28 day cycle.
Dose level 1 = 20 mg/m2 IV weekly on days 1, 8, and 15 of a 28 day cycle. Dose level 2 = 25 mg/m2 IV weekly on days 1, 8, and 15 of a 28 day cycle. Dose level 3 = 25 mg/m2 IV weekly on days 1, 8, and 15 of a 28 day cycle. Dose level 4 = 25 mg/m2 IV weekly on days 1, 8, and 15 of a 28 day cycle.
City of Hope Medical Center
Duarte, California, United States
South Pasadena Cancer Center
Pasadena, California, United States
Number of Participants With at Least One Dose Limiting Toxicity in Phase I
Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater non-hematologic toxicity (excluding alopecia, controllable nausea and vomiting, and serum triglycerides \< 1,500 mg/dL which recover within 1 week), grade 4 or greater thrombocytopenia, grade 4 or greater febrile neutropenia requiring hospitalization, or treatment delay of \> 2 weeks as a result of unresolved toxicity during the first cycle of therapy.
Time frame: 4 weeks from start of treatment, up to 2 years
Recommended Phase II Dose
The maximum tolerated dose (MTD) of Vinorelbine is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
Time frame: 4 weeks from start of treatment, up to 2 years
Progression-free Survival Rate at 4 Months
Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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 lesions.
Time frame: 4 months following the last course of treatment
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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 lesions.
Time frame: Until disease progression, up to 5 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate defined as percentage of patients achieving a Best Response of either CR or PR.
Time frame: After 2 cycles of treatment, up to 2 years.
Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Until death from any cause, up to 5 years.
Toxicity Profile
Number of Participants with Treatment-Related Grade 3 \& 4 Toxicities for Sorafenib and Vinorelbine Combination
Time frame: 28 days following the last course of treatment