Sorafenib and Ifosfamide in Treating Patients With High-Grade Soft Tissue Sarcoma or Bone Sarcoma That Can Be Removed by Surgery

OBJECTIVES:

Primary

- Assess the safety, toxicity, and efficacy of neoadjuvant sorafenib tosylate and
ifosfamide in patients with resectable high-grade soft tissue or bone sarcoma.

Secondary

- Assess the long-term efficacy or impact of therapy in these patients, in terms of the
duration of local recurrence-free survival, distant recurrence-free survival, and
disease-specific survival.

OUTLINE:

- Neoadjuvant therapy: Patients receive oral sorafenib tosylate twice daily on days 1-14
in course 1. Patients then receive oral sorafenib tosylate twice daily on days 1-28 and
ifosfamide IV continuously on days 1-7 in courses 2 and 3. Treatment repeats every
14-28 days* for 3 courses.

NOTE: *Course 1 is 14 days in duration; courses 2 and 3 are 28 days in duration.

- Surgery: At least 1 week after the completion of neoadjuvant therapy, patients undergo
surgery.

- Adjuvant therapy: Beginning ≥ 3 weeks after surgery, patients who respond to
neoadjuvant therapy receive oral sorafenib twice daily for 6 months. Patients also
receive 2 courses of ifosfamide as in courses 2 and 3 of neoadjuvant therapy.

Inclusion Criteria:

- Pathologically confirmed high grade sarcoma of the soft tissue or bone

- participants Identified as a proper candidate for ifosfamide-based neoadjuvant
therapy

- candidates must have operable disease for which a resection is planned

- ECOG performance status 0-1

- Hemoglobin ≥ 9.0 g/dL

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)

- INR < 1.5 or PT/PTT normal.Concurrent anticoagulation therapy with warfarin or
heparin allowed

- Creatinine ≤ 1.5 times ULN

- women of childbearing potential must have negative pregnancy test performed within 7
days prior to start of treatment.

- Fertile patients must use effective contraception during and for ≥ 2 weeks after
completion of study therapy.

- A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

- known HIV infection

- chronic hepatitis B or C infection

- clinically active serious infection > CTCAE grade 2

- NYHA class III or IV congestive heart failure

- unstable angina (i.e., anginal symptoms at rest) or new onset angina within the past
3 months

- myocardial infarction within the past 6 months

- cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or
diastolic BP > 90 mm Hg) despite optimal medical management

- thrombolic or embolic events (e.g., cerebrovascular accident, including transient
ischemic attacks) within the past 6 months

- pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks

- other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks

- Any condition that would impair the ability to swallow whole pills

- malabsorption problem

- Any known severe hypersensitivity to sorafenib tosylate or any of its excipients

- known or suspected allergy to sorafenib tosylate or any agent given in this study

- serious nonhealing wound, ulcer, or bone fracture

- evidence or history of bleeding diathesis or coagulopathy

- significant traumatic injury within the past 4 weeks

- major surgery or open biopsy within 4 weeks of starting treatment

- Concomitant St. John's wort or rifampin

- KNown brain metastases. Patients with neurological symptoms must undergo a CT
scan/MRI of the brain to exclude brain metastases.

- any condition that impairs patients' ability to swallow pills

- any malabsorption problem