S0505 Sorafenib in Treating Patients With Advanced Soft Tissue Sarcomas

Study Overview
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Brief Summary
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RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with advanced soft tissue sarcomas.

Detailed Description
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OBJECTIVES: Determine the objective response rate (confirmed, complete, and partial) in patients with advanced soft tissue sarcomas treated with sorafenib. Determine the 4-month progression-free survival rate in patients treated with this drug. Determine the frequency and severity of adverse events in patients treated with this drug. OTHER OBJECTIVES (if funding permits): Correlate, preliminarily, a decrease in standard uptake variable (SUV) of target lesions by positron-emission tomography scan at 4 weeks with response in patients treated with this drug. Correlate, preliminarily, the phosphorylation status of KIT, PDGFR, VEGFR, and the raf/mek/erk pathway with response in patients treated with this drug. Correlate, preliminarily, the most common B-raf kinase mutation with response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to histology (leiomyosarcoma vs liposarcoma vs angiosarcoma, hemangiosarcoma, or hemangiopericytoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 8 weeks until disease progression and then every 6 months for 2 years and annually for up to 3 years. PROJECTED ACCRUAL: A total of 45-75 patients (15-25 per stratum) will be accrued for this study within 15-38 months.

Official Title
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Phase II Trial of BAY-9006 (NSC #724772) in Advanced Soft Tissue Sarcomas

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma of 1 of the following histologies: Angiosarcoma, cutaneous or visceral Malignant hemangiosarcoma Malignant hemangiopericytoma Grade 3-4 leiomyosarcoma Grade 3-4 liposarcoma Must have evidence of unresectable residual disease, metastatic disease, or recurrent disease by radiography Measurable disease by x-ray, scans, or physical examination Archived paraffin-embedded tumor sections available No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases) Bilirubin normal (≤ 2.5 times ULN if due to liver metastases) PT, PTT, and INR normal Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular No history of thromboembolic disease No uncontrolled hypertension Other Not pregnant or nursing Fertile patients must use effective contraception Able to swallow oral medication No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 28 days since prior chemotherapy (42 days for carmustine or mitomycin) and recovered Prior adjuvant chemotherapy allowed No more than 1 prior chemotherapy regimen for metastatic disease Endocrine therapy Not specified Radiotherapy At least 28 days since prior radiotherapy and recovered Must have evidence of disease progression within, or measurable disease outside of, the radiation field after completion of radiotherapy Surgery At least 28 days since prior major surgery and recovered Other No prior sorafenib No prior inhibitor of VEGFR or MAPK pathway No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No concurrent therapeutic anticoagulation No concurrent administration of any of the following medications: Rifampin Hypericum perforatum (St. John's wort) Cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following: Phenytoin Carbamazepine Phenobarbital

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sorafenib<br>sorafenib | Drug: sorafenib<br>* 800 mg per day, daily until progression<br>* Other names: BAY 43-9006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Confirmed, Complete and Partial) | Partial response (PR) is greater than or equal to 30% decrease under baseline of sum of longest diameters of all target measurable lesions; No unequivocal progression of non-measurable disease; No new lesions. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration. Stable disease does not qualify for CR, PR, Progression or Symptomatic Deterioration. Progressive disease is any one or more of the following: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Assessment inadequate is progression or symptomatic deterioration has not been documented, and one or more target measurable lesions have not been assessed or inconsistent assessment methods were used. | Assessment performed every eight weeks until progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Four-month Progression-free Survival Rate |  | 0 - 4 months | 
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 - Severe, Grade 4 - Life-threatening, Grade 5 - Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported. | Patients were assessed for adverse events two weeks after starting protocol treatment and then after every cycle of treatment (1 cycle = 28 days) for the duration of protocol treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult angiosarcoma, adult leiomyosarcoma, adult liposarcoma, adult malignant hemangiopericytoma, recurrent adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma