Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma

Study Overview
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Brief Summary
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This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity. All patients with unresectable or metastatic soft tissue sarcoma (STS): leiomyosarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH) seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.

Detailed Description
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This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate, an oral multi-kinase inhibitor. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity which in the opinion of the treating physician or the trial Principal Investigator (PI) compromises the ability of the patient to receive treatment or the patient desires to stop treatment. All patients with unresectable or metastatic STS: leiomyosarcoma, liposarcoma, fibrosarcoma, and MFH seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study. An office visit will be required before the beginning of every cycle every 6 weeks to assess toxicity and for physical examination. Complete blood count (CBC) and differential, comprehensive metabolic panel, and electrocardiogram (ECG) will be obtained at every scheduled visit.

Official Title
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Phase II Open-Label Study of Sunitinib Malate (SU011248) in Adult Patients With Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma

Conditions
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Liposarcoma, Leiomyosarcoma, Fibrosarcoma, Malignant Fibrous Histiocytoma

Intervention / Treatment
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* Drug: Sunitinib Malate (SU011248)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1. Adequate organ function as defined by the following criteria: Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin less than or equal to 1.5 x ULN Absolute neutrophil count (ANC) greater than or equal to1500/microL Platelets greater than or equal to 100,000/microL Hemoglobin greater than or equal to 9.0 g/dL Serum calcium less than or equal to 12.0 mg/dL Serum creatinine less than or equal to 1.5 x ULN Histologically-proven liposarcoma, leiomyosarcoma, fibrosarcoma, or MFH Measurable disease radiographically Disease that is deemed surgically unresectable and/or metastatic Age greater than or equal to 18 years Life expectancy greater than 16 weeks Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Patients may have had up to 3 prior chemotherapies within 4 weeks of starting the study treatment. Exclusion Criteria: Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the study treatment. NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease. Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism Ongoing cardiac dysrhythmias of NCI CTCAE greater than or equal to grade 2 Prolonged QTc interval on baseline electrocardiogram (ECG) > 500 msec. Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy) Prior tyrosine kinase inhibitor therapy Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection Concurrent treatment on another clinical trial, except supportive care or non-treatment trials Concomitant use of agents known to induce or inhibit CYP3A4 Concomitant use of agents metabolized by the cytochrome P450 system Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg by mouth [PO] daily for thrombo-prophylaxis is allowed) Pregnancy or breastfeeding patients Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.

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: Sunitinib Malate (SU011248) Treatment<br>Sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks | Drug: Sunitinib Malate (SU011248)<br>* For each 6 week cycle, patients will take SU011248 every day in the morning for 4 weeks followed by a 2 week rest period.<br>* Other names: SU011248;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response (OR) | Objective Radiographic Response Rate. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST). | From On Treatment to Off Study - average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants' Progression Free Survival (PFS) | Time to tumor progression defined as the duration of time from start of treatment to time of progression. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST). | From On Treatment to Off Study - average of 6 months | 
| Participants' Overall Survival (OS) | The median OS times (months) for liposarcoma, leiomyosarcoma and MFH. | From On Treatment to Off Study - average of 6 months | 
| Number of Participants With Serious Adverse Events (SAEs) | Determine the number of participants who experience Serious Adverse events while on sunitinib malate study. | 4 years, 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sunitinib malate, SUTENT, SU011248, Soft tissue sarcoma, Gastrointestinal stromal tumors (GIST), MFH, Tyrosine kinase inhibitor, Imatinib mesylate, Phase II