Sorafenib, Epirubicin, Ifosfamide, and Radiation Therapy Followed By Surgery in Treating Patients With High-Risk Stage II or Stage III Soft Tissue Sarcoma

• Status: Completed
• Trial end date: 2013-04-30
• Target enrollment: 0
• Participant gender: All

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 epirubicin and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with epirubicin, ifosfamide, and radiation therapy followed by surgery in treating patients with high-risk stage II or stage III soft tissue sarcoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Epirubicin; Ifosfamide; Isophosphamide mustard; Niacinamide; Sorafenib

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed soft tissue sarcoma of the upper (including shoulder) or lower (including hip) extremities or body wall

• Stage II or III disease, as defined by the following:

• Tumor dimension > 5 cm

• Superficial or deep tumor

• Intermediate or high-grade disease

• No regional lymph node involvement

• No distant metastases

• No rhabdomyosarcoma, Ewing sarcoma, primitive neuroectodermal tumor (PNET), osteosarcoma, or gastrointestinal stromal tumor

• Pleomorphic rhabdomyosarcoma allowed

• No known metastases

• Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastases

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Absolute Neutrophil Count (ANC) ≥ 1,500/μL

• Hemoglobin ≥ 9.0 g/dL

• Platelet count ≥ 100,000/μL

• International Normalized Ratio (INR) < 1.5 or Prothrombin Time/Partial Thromboplastin Time (PT/PTT) normal

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 mg/dL

• Aspartate Aminotransferase/Alanine Aminotransferase (AST/ALT) ≤ 1.5 times ULN

• Left Ventricular Ejection Fraction (LVEF) ≥ 50%

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception (male patients must use effective contraception for ≥ 3 months after completion of study treatment)

• No contraindications to limb-sparing surgery

• No severe peripheral vascular disease

• No concurrent uncontrolled illness including, but not limited to, the following:

• Ongoing or active serious infection > Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2

• Symptomatic congestive heart failure

• Unstable angina pectoris (i.e., angina symptoms at rest) or new onset angina within the past 3 months

• Myocardial infarction within the past 6 months

• Cardiac ventricular arrhythmia requiring anti-arrhythmic therapy

• Psychiatric illness/social situation that would limit compliance with study requirements

• No uncontrolled hypertension (defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg, despite optimal medical management)

• No known HIV infection or chronic hepatitis B or C infection

• No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months

• No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks

• No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks

• No serious non-healing wound, ulcer, or bone fracture

• No evidence or history of bleeding diathesis or coagulopathy

• No significant traumatic injury within the past 4 weeks

• No known or suspected allergy to sorafenib tosylate or any agent given in the study

• No condition that would impair the ability to swallow whole pills

• No malabsorption problem

• No "currently active" second malignancy other than non-melanoma skin cancer

• Not considered to have a "currently active" malignancy if patient completed therapy AND has a < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or biotherapy

• More than 4 weeks since prior major surgery

• No concurrent St. John's wort or rifampin

• No other concurrent investigational or anticancer therapy

• Concurrent anticoagulation with warfarin or heparin allowed