This phase II trial studies how well sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery work in treating patients with high-risk stage IIB-IV soft tissue sarcoma. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin hydrochloride and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery may be an effective treatment for soft tissue sarcoma.
PRIMARY OBJECTIVES: I. To determine the pathologic response rate (\>= 95% necrosis) after preoperative treatment with sorafenib (sorafenib tosylate), epirubicin (epirubicin hydrochloride), ifosfamide, and hypofractionated radiation for high risk soft tissue sarcomas of the extremities or body wall. SECONDARY OBJECTIVES: I. To further characterize the safety of sorafenib plus chemoradiotherapy, including wound complication rate. II. To estimate time-to-event rates, including overall survival, overall disease-free survival, distant disease-free survival, and local disease-free survival in patients with high risk soft tissue sarcomas of the extremities or body wall treated with preoperative sorafenib plus chemoradiotherapy and postoperative sorafenib plus chemotherapy. OUTLINE: Patients receive sorafenib tosylate orally (PO) once daily (QD) on days 1-71 and 85-155, epirubicin hydrochloride intravenously (IV) over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo external beam radiation therapy (EBRT) on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98. After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given IV
Undergo EBRT
Given IV
Correlative studies
Given PO
Undergo surgical resection
OHSU Knight Cancer Institute
Portland, Oregon, United States
Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.
Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.
Time frame: Assessed at surgical resection
Number of Grade 3-4 Adverse Events
Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Time frame: Up to 5 years
Number of Participants With Wound Complications
Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.
Time frame: At least 120 days
Overall Survival at 2 Years
Percentage of patients alive at 2 years, Method of Kaplan-Meier used.
Time frame: Time from registration until death from any cause
Overall Disease-free Survival (Stage IIB-III Patients)
Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \\used.
Time frame: Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years
Distant Disease-free Survival (Stage IIB-III Patients)
Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.
Time frame: Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years
Number of Participants With Local Recurrence
Number of patients with local recurrence after surgical resection of the primary tumor
Time frame: Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)
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