Sorafenib Tosylate, Combination Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With High-Risk Stage IIB-IV Soft Tissue Sarcoma
Condition: Pleomorphic Rhabdomyosarcoma; Stage IIB Adult Soft Tissue Sarcoma AJCC v7; Stage III Adult Soft Tissue Sarcoma AJCC v7; Stage IV Adult Soft Tissue Sarcoma AJCC v7
MeSH terms: Sarcoma; Rhabdomyosarcoma
Intervention: Epirubicin Hydrochloride; External Beam Radiation Therapy; Ifosfamide; Laboratory Biomarker Analysis; Sorafenib Tosylate; Therapeutic Conventional Surgery
Intervention description: Given IV; Undergo EBRT; Given IV; Correlative studies; Given PO; Undergo surgical resection
Intervention MeSH terms: Sorafenib; Epirubicin; Ifosfamide; Isophosphamide mustard
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed, soft-tissue sarcoma: excluding rhabdomyosarcoma (pleomorphic
             rhabdomyosarcoma patients are eligible), Ewing's, primitive neuroectodermal tumor
             (PNET), osteosarcoma, or gastrointestinal stromal tumor

          -  American Joint Committee on Cancer (AJCC) (7th edition) stage IIb, III, or IV patients
             planned for resection of the primary tumor

               -  > 5 cm in greatest dimension

               -  Intermediate or high-grade

               -  Superficial or deep

          -  Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on
             body wall

          -  Intermediate or high-grade: grades 2 or 3 on scale of 1-3

          -  Left ventricular ejection fraction (LVEF) >= 50%

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Hemoglobin (Hgb) >= 9.0 g/dL

          -  Platelets >= 100,000/uL

          -  Creatinine =< 1.5 x upper limit of normal (ULN)

          -  Bilirubin =< 1.5 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x ULN

          -  International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial
             thromboplastin time (PTT) within normal limits; patients receiving anti-coagulation
             treatment with an agent such as warfarin or heparin may be allowed to participate; for
             patients on warfarin, the INR should be measured prior to initiation of sorafenib and
             monitored at least weekly, or as defined by the local standard of care, until INR is
             stable

          -  No prior chemotherapy, radiation, or biotherapy

          -  No major surgery within 4 weeks prior to study entry

          -  No contraindications to limb-sparing surgery; patient should be evaluated by a surgeon
             who specializes in sarcoma resections prior to study enrollment to ensure patient (pt)
             is a candidate for limb-sparing surgery

          -  No severe peripheral vascular disease

          -  Adequate contraception must be used and patients must not be pregnant or
             breastfeeding; women of childbearing potential and men must agree to use adequate
             contraception (barrier method of birth control) prior to study entry and for the
             duration of study participation; men and women should use adequate birth control for
             at least thirty days after the last administration of sorafenib

          -  Women of childbearing potential must have negative serum pregnancy test performed
             within 7-days prior to registration

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

          -  Patient must sign a study-specific consent form prior to registration

          -  Ability to understand and the willingness to sign a written informed consent; a signed
             informed consent must be obtained prior to any study specific procedures

        Exclusion Criteria:

          -  Patients with known brain metastases; patients with neurological symptoms must undergo
             a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to
             exclude brain metastases

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular
             arrhythmia requiring anti-arrhythmic therapy, or psychiatric illness/social situations
             that would limit compliance with study requirements; patients must not have unstable
             angina (angina symptoms at rest) or new onset angina (began within the last 3 months)
             or myocardial infarction within the past 6 months

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management

          -  Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

          -  Thrombolic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months

          -  Pulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first dose of
             study drug

          -  Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of
             study drug

          -  Serious non-healing wound, ulcer, or bone fracture

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Major surgery or significant traumatic injury within 4 weeks of first study drug

          -  Use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers

          -  Known or suspected allergy to sorafenib or any agent given in the course of this trial

          -  Any condition that impairs patient's ability to swallow whole pills

          -  Any malabsorption problem

          -  Pregnant or lactating women are excluded from this study

          -  Patients with a "currently active" second malignancy other than non-melanoma skin
             cancers are not to be registered; patients are not considered to have a "currently
             active" malignancy if they have completed therapy and considered by their physician to
             be at less than 30% risk of relapse

          -  Any uncontrolled thyroid disease

          -  Requirement for hemodialysis or peritoneal dialysis