Nintedanib in Treating Patients with Malignant Pleural Mesothelioma That Is Recurrent or Cannot Be Removed by Surgery

Inclusion Criteria

• Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma
• Patients must have measurable or non-measurable disease documented by computed tomography (CT) scan; measurable disease must be assessed within 28 days prior to registration; non-measurable disease must be assessed within 42 days prior to registration; the CT from a combined positron emission tomography (PET)/CT must not be used to document measurable disease unless it is of diagnostic quality; all disease must be assessed by RECIST and modified RECIST criteria
• Patients must have had prior systemically administered platinum-based chemotherapy; pleural space washing with cisplatin does not constitute systemic administration; no more than two prior systemic therapeutic regimens are allowed (including biologics, targeted therapies), and at least one regimen must have been platinum-based; immunotherapy will not be counted as a prior regimen; neoadjuvant and/or adjuvant systemic therapy will not be counted as a prior regimen, assuming at least 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy and development of progressive disease; patients must have completed systemic therapy (including any chemotherapy, biologics, targeted and immunotherapies) >= 28 days (42 days for nitrosoureas or mitomycin C) prior to registration and have recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered
• No prior treatment with BIBF 1120 or any other vascular endothelial growth factor receptor (VEGFR) inhibitor, not including bevacizumab
• No known hypersensitivity to BIBF 1120, to its excipients or to contrast media
• Patients may have received prior surgery (e.g., pleurectomy) provided that at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered (i.e., =< grade 1 or at baseline) from all associated toxicities at the time of registration; there must be no anticipated need for major surgical procedures during protocol treatment
• No active brain metastases (e.g. stable for < 4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before treatment); no leptomeningeal disease
• No radiographic evidence of cavitary or necrotic tumors
• No centrally located tumors with radiographic evidence (CT or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
• Institutions must offer patients the opportunity to submit tissue for future correlative studies
• Patients may have received prior definitive radiation therapy provided that at least 28 days (14 days for palliative radiation therapy) have elapsed since the last treatment and patients have recovered (i.e., =< grade 1 or at baseline) from all associated toxicities at the time of registration
• Patients must have a Zubrod performance status of 0-1
• Absolute neutrophil count (ANC) >= 1,500/mcl
• Hemoglobin (Hgb) > 9 g/dl
• Platelet count >= 100,000/mcl
• Serum bilirubin =< institutional upper limit of normal (IULN)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) must be =< 1.5 x IULN; for patients with liver metastasis, NO total bilirubin outside of normal limits, and NO ALT or AST > 2.5 ULN
• Serum creatinine =< 1.5 x IULN or a calculated or measured creatinine clearance >= 50 mL/min; these tests (including creatinine [mg/dl] if using calculated creatinine clearance) must be obtained within 14 days prior to registration
• No proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
• No therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day); no history of clinically significant hemorrhagic or thromboembolic event in the past 6 months
• No patients will have coagulation parameters: international normalized ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% deviation of the institutional ULN
• Patients must have no evidence of bleeding diathesis or coagulopathy; patients must have no pathologic condition other than mesothelioma that carries a high risk of bleeding
• No major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
• Patients must not have gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for intravenously (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
• No significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > [New York Heart Association NYHA] II, serious cardiac arrhythmia, pericardial effusion)
• No active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
• No active or chronic hepatitis C and/or B infection
• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method
• Contraception in patients with preserved reproductive capacity; patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or postmenopausal for at least two years; women of childbearing potential who are sexually active and not using a highly effective method of birth control during the trial and for at least three months (in case of monotherapy with BIBF 1120) after the end of active therapy are not allowed to participate in the trial; a highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
• No psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
• No active alcohol or drug abuse
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines