Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
Condition: Epithelioid Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatoid Mesothelioma; Stage II Pleural Mesothelioma; Stage III Pleural Mesothelioma; Stage IV Pleural Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms
Intervention: Laboratory Biomarker Analysis; Tivantinib
Intervention description: Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well tivantinib works in treating patients with previously
      treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed malignant pleural or
             peritoneal mesothelioma, epithelial, sarcomatoid, or mixed subtype; the patient's
             disease must be metastatic, recurrent, or unresectable

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
             resonance imaging (MRI), or calipers by clinical exam; pleural effusions and ascites
             are not considered measurable lesions

          -  No more than two prior cytotoxic chemotherapy regimens; prior chemotherapy with
             pemetrexed is required; prior intrapleural cytotoxic agents (including bleomycin) are
             allowed, and are not counted as a cytotoxic chemotherapy; chemotherapy must have been
             completed at least 4 weeks prior; patients who have previously received radiation
             therapy are eligible provided that the only site of measurable disease is not located
             within the radiation therapy port; at least 4 weeks must have elapsed from completion
             of the radiation therapy and all signs of toxicity must have resolved

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

          -  Life expectancy of greater than 3 months

          -  Hemoglobin >= 9.0 g/dL

          -  White blood cells (WBC) >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 X institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal

          -  Serum creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance
             >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  The effects of ARQ 197 on the developing human fetus are unknown; for this reason and
             because tyrosine kinase inhibitors as well as other therapeutic agents used in this
             trial are known to be teratogenic, women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation; should a
             woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately; men
             treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of study participation, and 4 months after
             completion of ARQ 197 administration

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events (to grade =< 1) due to agents administered more than 4
             weeks earlier

          -  Patients who are receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ARQ 197

          -  ARQ 197 is metabolized by cytochrome P450 (CYP)2C19, and to a lesser extent CYP3A4;
             the metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered
             by inhibitors and/or inducers or other substrates of CYP2C19 and CYP3A4; while
             inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded,
             investigators should be aware that ARQ 197 exposure may be altered by the concomitant
             administration of these drugs; because the lists of these agents are constantly
             changing, it is important to regularly consult a frequently-updated list; as part of
             the enrollment/informed consent procedures, the patient will be counseled on the risk
             of interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal
             product

          -  History of congestive heart failure defined as Class II to IV per New York Heart
             Association (NYHA) classification; active coronary artery disease (CAD); clinically
             significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade
             3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction
             occurring within 6 months prior to study entry (myocardial infarction occurring > 6
             months prior to study entry is permitted)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study because ARQ 197 is a tyrosine kinase
             inhibitor with the potential for teratogenic or abortifacient effects; because there
             is an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with ARQ 197, breastfeeding should be discontinued if the
             mother is treated with ARQ 197

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetic interactions with
             ARQ197; in addition, these patients are at increased risk of lethal infections when
             treated with marrow-suppressive therapy; appropriate studies will be undertaken in
             patients receiving combination antiretroviral therapy when indicated

          -  No prior treatment with a c-MET inhibitor