Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients With Soft Tissue Sarcoma of the Extremity and Body Wall

• Status: Completed
• Trial end date: 2011-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients will receive neoadjuvant sorafenib (investigational agent) in combination with preoperative external beam conformal radiotherapy (50 Gy in 25 fractions) for localized, large soft tissue sarcomas of the extremity and body wall prior to resection with curative intent. Sorafenib is an FDA-approved targeted agent for patients with renal cell carcinoma and hepatocellular carcinoma. Preliminary data suggest activity for sorafenib against soft tissue sarcoma in the metastatic setting. Limited data are available regarding the safety and efficacy of sorafenib in combination with radiotherapy.

The Phase I portion of the trial will seek to establish the safety of sorafenib and radiotherapy in the neoadjuvant setting for soft tissue sarcomas of the extremity and body wall. The Phase II portion of the trial will aim to determine the pathologic near-complete/complete response rate (≥ 95% tumor necrosis) of this multimodality therapy. Molecular and dynamic contrast-enhanced MRI studies will seek to establish correlative biological and imaging markers of response and/or resistance to this therapy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Davis
• Collaborator: Bayer
• Treatments: Sorafenib

Criteria

Inclusion Criteria:

• Histologically confirmed soft-tissue sarcoma located on the extremity or body wall.

• Intermediate or High grade (NCI grade 2 or 3/3-tier system), > 5 cm in maximal dimension.

• Low grade (NCI grade 1/3-tier system), > 8 cm in maximal dimension.

• No evidence of regional or distant metastatic disease.

• Patient must be 18 years of age or older.

• Patient must have an ECOG performance status of ≤ 2.

• Patient must have a histologic diagnosis of soft tissue sarcoma.

• Patient must have adequate bone marrow, liver, and renal function as assessed by the following:

• Hemoglobin ≥ 9.0 g/dl

• Absolute neutrophil count (ANC) ≥ 1,500/mm3

• Platelets ≥ 100,000/mm3.

• Total bilirubin ≤ 1.5 mg/dL. NOTE: Patients with elevated bilirubin secondary to Gilbert's syndrome are eligible to participate in the study.

• AST and ALT ≤ 2.5 times the institution upper limit of normal (ULN).

• Creatinine ≤ 1.5 times ULN.

• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the start of treatment . NOTE: Postmenopausal women must be amenorrheic for at least 12 months to be deemed not of reproductive potential.

• 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 should use adequate birth control for at least three months after the last administration of sorafenib.

• 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.

• INR < 1.5 or a PT/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.

Exclusion Criteria:

• Patient is receiving additional cancer-directed therapy at time of entry into trial.

• Patient has received or is receiving preoperative investigational treatment.

• Patient has congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.

• Patient has history of cardiac ventricular arrhythmia requiring ongoing anti-arrhythmic therapy.

• Patient has uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.

• Patient has known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

• Patient has active clinically serious infection > CTCAE Grade 2.

• Patient has thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• Patient has history of pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.

• Patient has history of any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.

• Patient has history of clinical or laboratory evidence of bleeding diathesis or coagulopathy.

• Patient has history of major surgery or significant traumatic injury within 4 weeks of first study drug.

• Patient has concomitant use of St. John's Wort or rifampin (rifampicin).

• Patient has known or suspected allergy to sorafenib or any agent given in the course of this trial.

• Patient has any condition that impairs his or her ability to swallow whole pills.