Sunitinib in Treating Patients With Advanced Malignant Pleural Mesothelioma

Study Overview
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Brief Summary
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This phase II trial is studying how well sunitinib works in treating patients with advanced malignant mesothelioma of the pleura. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the efficacy of sunitinib malate, in terms of response rate (complete and partial), in patients with malignant pleural mesothelioma. II. Assess the toxicity, safety, and tolerability of this drug in these patients. III. Assess the duration of response or stable disease, stable disease rate, progression-free survival, and median and overall survival rates. OUTLINE: This is a multicenter, nonrandomized, open-label study. Patients are stratified according to prior cytotoxic chemotherapy (yes vs no). Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Official Title
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A Phase II Study of Sunitinib (SU11248; NSC 736511; IND 74019) in Patients With Advanced Malignant Pleural Mesothelioma

Conditions
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Advanced Malignant Mesothelioma, Recurrent Malignant Mesothelioma

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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Criteria: Histologically or cytologically confirmed malignant pleural mesothelioma; Advanced or metastatic disease incurable by standard therapies Measurable disease, defined as at least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan; No sole site of disease in a previously irradiated area unless there has been subsequent evidence of progression; Low-dose, palliative radiotherapy allowed Meets 1 of the following criteria for prior cytotoxic chemotherapy treatment: Previously treated with 1 platinum-based chemotherapy regimen; Previously untreated (i.e., no prior cytotoxic chemotherapy) No known brain metastases ECOG performance status 0-1 Life expectancy >= 12 weeks Platelet count >= 100,000/mm^3 Absolute granulocyte count >= 1,500/mm^3 Bilirubin normal AST and ALT =< 2.5 times upper limit of normal Calcium =< 3 mmol/L Creatinine normal OR creatinine clearance >= 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Patients must reside within a 1.5 hour drive from participating center Able to take oral medication No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix, or any other curatively treated solid tumor No known history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate No QTc prolongation (i.e., QTc interval >= 500 msec) or other significant ECG abnormalities No New York Heart Association (NYHA) class III or IV heart failure Patients with the following histories allowed provided they are asymptomatic with respect to cardiac function and LVEF is normal by MUGA at baseline: Anthracycline exposure, Central thoracic radiation that included the heart, NYHA class II cardiac function No uncontrolled hypertension (i.e., systolic blood pressure >= 140 mm Hg or diastolic blood pressure >= 90 mm Hg) No cardiac disease within the past 12 months, including any of the following: myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure No pulmonary embolism within the past 12 months No cerebrovascular accident or transient ischemic attack within the past 12 months No bowel obstruction or any condition that would impair the ability to swallow and retain sunitinib malate, including any of the following: gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, active peptic ulcer disease No serious illness or medical condition that would preclude study treatment including, but not limited to, any of the following: history of significant neurologic or psychiatric disorder that would impair the ability to obtain consent or limit compliance with study requirements, Active uncontrolled infection, Any other medical condition that might be aggravated by treatment, OR; Serious or nonhealing wound, ulcer, or bone fracture, Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days No pre-existing hypothyroidism unless euthyroid on medication At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: Azole antifungals (e.g., ketoconazole, itraconazole, miconazole), Verapamil, Clarithromycin, HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir) Erythromycin, Delavirdine, Diltiazem At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: Rifampin, Phenytoin, Rifabutin, Hypericum perforatum (St. John's wort), Carbamazepine, Efavirenz Phenobarbital, Tipranavir At least 4 weeks since prior major surgery and recovered At least 4 weeks since prior radiotherapy and recovered At least 12 months since prior coronary/peripheral artery bypass graft or stenting No prior surgical procedures affecting absorption No prior radiotherapy that involved >= 30% of functioning bone marrow No prior treatment with any other antiangiogenic agents or multitargeted tyrosine kinase inhibitors, including any of the following: bevacizumab, sorafenib tosylate, pazopanib, thalidomide, AZD2171, vandetanib, AMG706, vatalanib, VEGF Trap No prior angiogenesis inhibitors except epidermal growth factor receptor inhibitors or other noncytotoxic therapy No other concurrent anticancer therapy or treatment with other investigational anticancer agents No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin); Doses =< 2 mg/day for prophylaxis of thrombosis or low molecular weight heparin for patients with an INR < 1.5 are allowed No concurrent agents with proarrhythmic potential, including any of the following: terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide

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: Treatment (sunitinib malate)<br>Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: sunitinib malate<br>* Given orally<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Partial and Complete) Per RECIST | Number of patients who had objective responses after radiology review | Up to 3 years |