A Phase II Study of Single-agent DOVitinib in Advanced Malignant PlEural Mesothelioma Which Has Progressed Following Prior Platinum-Antifolate Chemotherapy

Inclusion Criteria: * Advanced incurable histologically confirmed malignant pleural mesothelioma that has progressed following prior administration of platinum-antifolate based chemotherapy. * Measurable disease by RECIST 1.1. For those patients with only pleural rind, measurable disease will be determined using modified RECIST criteria. * Availability of archival tissue. Exclusion Criteria: * Less than 18 years of age. * ECOG performance status \> 2. * Received \> two lines of systemic therapy. * Patients who have received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosureas and mitomycin-C) ≤ 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy. * Patients who have received the last administration of nitrosureas or mitomycin-C ≤ 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy. * Patients who have received radiotherapy ≤ 4 weeks prior to starting the study drug or who have not recovered from radiotherapy-related toxicities (note: palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study drug is allowed). * Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal, intra-pelvic) ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such surgery. * Prior use of angiogenesis inhibitors. * Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated cancer such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer or in-situ carcinoma of the uterine cervix. (Exception, patients with localized prostate cancer treated within the last 2 years and currently on hormonal therapy). * Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) ≤ 6 months prior to starting study drug. * Cirrhosis of the liver or known hepatitis B or C infection that is either acute or is considered chronic because the virus did not become undetectable: 1. Hepatitis C Virus (HCV) infection: acute or chronic infection as depicted by a positive HCV RNA testing (note: in a patient with known anti-HCV but with a negative test for HCV RNA, re-testing for HCV RNA 4-6 months later is requested to confirm the resolution of HCV infection) 2. Hepatitis B Virus (HBV) infection: acute infection (HBsAg+ with or without HBeAg+ or detectable serum HBV DNA), HBV carriers as evidence by ongoing presence of HBsAg and detectable serum HBV DNA levels * Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory). * Patients who are currently receiving antiplatelet therapy of prasugrel or clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. However, treatment with low doses of warfarin (e.g., ≤ 2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) to prevent cardiovascular events or strokes is allowed. Required use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin, although doses of up to 2mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided the patient's PT INR is \< 1.5. * Urine dipstick reading: Positive for proteinuria or, if documentation of +1 results for protein on dipstick reading, then total urinary protein \>500 mg and measured creatinine clearance \<50 mL/min/1.73m2 from a 24 hour urine collection. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to dovitinib. * Taking medications that are potent CYP3A4 inducers or inhibitors (dovitinib is metabolized primarily by the CYP3A4 liver enzyme, every effort should be made to switch patients taking such agents or substances to other medications). * History of cardiac dysfunction with an ECHO or MUGA scan outside the institutional range of normal for patients with impaired cardiac function or clinically significant cardiac disease, including any of the following: 1. History or presence of serious uncontrolled ventricular arrhythmias 2. Clinically significant resting bradycardia 3. LVEF assessed by either 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) \< 45% or lower limit of normal (whichever is the higher) 4. Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic Attack (TIA) 5. Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s). Initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry * Pre-existing condition (e.g., gastrointestinal tract disease), resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease that impairs the ability to swallow and retain dovitinib tablets. * Pre-existing thyroid abnormality with an inability to maintain thyroid function in the normal range with medication. * Patients with any of the following conditions: 1. Clinically significant pulmonary or GI bleeding of greater than 30 cc in the preceding 3 months 2. Serious or non-healing wound, ulcer, or bone fracture, 3. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment. * Patients with brain metastases. * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol. * Any abnormal organ and marrow function as defined below: 1. Leukocytes \<3,000/microL 2. Absolute neutrophil count \<1,500/microL 3. Platelets \<100,000/microL 4. Total bilirubin \>1.5X institutional upper limit of normal (ULN) 5. AST(SGOT) / ALT(SGPT) \>2.5X institutional ULN 6. Amylase/lipase outside normal institutional limits 7. Serum creatinine \>1.5X ULN or Creatinine clearance \<60mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Pregnant or lactating women. * Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception. Note: Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes (female patients and their male partners) during the study and 30 days after the end of study treatment. Contraceptives that are affected by cytochrome P450 interactions (e.g. oral, implantable, injectable, or intrauterine hormonal contraceptives) are not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug. * Fertile males not willing to use contraception. Note: Fertile males must use condom with spermicide. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes (male patients and their female partners) during the study and 30 days after the end of study treatment. * Psychiatric illness/social situations that would limit compliance with study requirements. * Receiving any other investigational agent(s). * Patients unwilling or unable to comply with the protocol. * Inability to understand or unable to provide written informed consent.