Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Sorafenib may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and blocking some of the enzymes needed for tumor cell growth.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with soft tissue sarcoma.

Further Study Information

OBJECTIVES:

Primary

• Determine if sorafenib can decrease interstitial fluid pressure in patients with soft tissue sarcomas.

• Determine the effects of this drug on tumor blood flow, circulating endothelial cells, vascular density, and pericyte coverage in these patients.

• Determine the pharmacokinetics of this drug in these patients.

Secondary

• Determine, preliminarily, any evidence of antitumor activity of this drug in these patients.

• Determine if there are any significant relationships between systemic drug exposure and drug-related toxicity or biological effect in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are assigned to one of two groups (group 1 closed to accrual as of 5/30/07).

• Group I (sarcomas of the extremity) (closed to accrual as of 5/30/07): Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.

• Group II (metastatic or inoperable sarcomas): Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.

In both groups, blood samples are drawn periodically for pharmacological studies.

After completion of study therapy, patients are followed monthly until all study-related toxicities are resolved and then at the discretion of the investigator.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of bone or soft tissue sarcoma, meeting 1 of the following criteria:

• Extremity sarcoma for which surgery is planned (closed for accrual as of 5/30/07)

• No osteosarcoma or Ewing's sarcoma that is potentially curable with surgery, chemotherapy, and/or radiotherapy

• Metastatic or inoperable sarcoma for which no known curative or survival-prolonging palliative therapy exists OR these therapies have failed

• At least 1 palpable tumor mass ≥ 2 cm in diameter with no overlying viscera which is amenable to biopsy

• At least 1 site of measurable disease that has not been previously irradiated

• Tumor amenable to serial biopsy and measurement of interstitial fluid pressure without excess risk to the patient

• Treated and/or stable, asymptomatic brain metastasis allowed

• No active brain metastasis, including any evidence of cerebral edema by CT scan or MRI, progression from prior imaging study, any requirement for steroids or enzyme-inducing anticonvulsant agents, or clinical symptoms from brain metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 2 months

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/ mm^3

• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)

• Bilirubin normal

• Creatinine ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled serious medical or psychiatric illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• At least 3 weeks since prior and no concurrent radiotherapy

• Concurrent adjuvant radiotherapy after surgery allowed (for patients with extremity sarcoma)

• At least 3 weeks since prior major surgery unrelated to sarcoma

• No prior sorafenib or other specific inhibitors of mitogen-activated kinase pathways

• No other concurrent investigational agents

• Concurrent warfarin anticoagulation therapy allowed provided all of the following criteria are met:

• On a stable dose

• INR target range is ≤ 3

• INR is monitored weekly

• Converted to a low molecular weight heparin (e.g., enoxaparin) from study entry until ≥ day 56

• No active bleeding or pathological condition that carries a high risk of bleeding

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent Hypericum perforatum (St. John's wort)

• No concurrent rifampin

• No concurrent grapefruit juice

Trial Contact Information

Trial Lead Organizations/Sponsors

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Jeffrey A. Morgan

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00330421
Information obtained from ClinicalTrials.gov on December 14, 2011

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