Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Closed 18 and over NCI DFCI-05033 NCI-6948, 6948, NCT00330421

Objectives

Primary

1. Determine if sorafenib can decrease interstitial fluid pressure in patients with soft tissue sarcomas.
2. Determine the effects of this drug on tumor blood flow, circulating endothelial cells, vascular density, and pericyte coverage in these patients.
3. Determine the pharmacokinetics of this drug in these patients.

Secondary

1. Determine, preliminarily, any evidence of antitumor activity of this drug in these patients.
2. Determine if there are any significant relationships between systemic drug exposure and drug-related toxicity or biological effect in patients treated with this drug.

Entry 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

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

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 2 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/ mm³
• 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

Expected Enrollment

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

Outcomes

Antivascular markers

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.

Trial Contact Information

Trial Lead Organizations

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

Jeffrey Morgan, MD, Principal investigator		Ph: 617-632-5204; 866-790-4500

Registry Information
Official Title		A Phase II Clinical and Correlative Study of BAY43-9006 (Sorafenib) IND 69,896 in Sarcoma
Trial Start Date		2006-06-01
Trial Completion Date		2007-11-23 (estimated)
Registered in ClinicalTrials.gov		NCT00330421
Date Submitted to PDQ		2006-01-11
Information Last Verified		2007-12-12
NCI Grant/Contract Number		CA62490, CA06516

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