Nintedanib in Treating Patients With Malignant Pleural Mesothelioma That Is Recurrent

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well nintedanib works in treating patients with malignant pleural mesothelioma that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To assess the 4-month progression-free survival (PFS) in patients with recurrent, unresectable malignant pleural mesothelioma (MAM) treated with nintedanib. SECONDARY OBJECTIVES: I. To assess response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in the subset of patients with measurable disease by both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria and Modified RECIST criteria for pleural tumors. II. To assess overall survival. III. To evaluate the frequency and severity of toxicities associated with this treatment regimen. IV. To collect tissue samples for future correlative studies related to overall study objectives. OUTLINE: Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Official Title
-----------------
A Phase II Trial of BIBF 1120 (Nintedanib) in Recurrent Malignant Pleural Mesothelioma

Conditions
-----------------
Recurrent Pleural Malignant Mesothelioma, Stage IV Pleural Mesothelioma

Intervention / Treatment
-----------------
* Drug: Nintedanib


Participation Criteria
=================
Eligibility Criteria
-----------------
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 and immunotherapies), and at least one regimen must have been platinum-based; 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 from adverse events due to agents administered No prior treatment with BIBF 1120 or any other vascular endothelial growth factor receptor (VEGFR) inhibitor 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 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 randomization); 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 radiation therapy provided that at least 14 days have elapsed since the last treatment and patients have recovered 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 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 using the following formula: calculated creatinine clearance = (140-age) x wt (weight) (kg) x 0.85 (if female)/72 x creatinine (mg/dl); 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 < 325mg per day); no history of clinically significant haemorrhagic or thromboembolic event in the past 6 months 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 > NYHA [New York Heart Association Class] 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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (nintedanib)<br>Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Nintedanib<br>* Given PO<br>* Other names: Vargatef;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months). | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade 3-4 Toxicity | Number of participants with grade 3 or grade 4 for each type of toxicity encountered, using all toxicity evaluable patients. | Up to 1 year | 
| Overall Survival | Overall survival will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months). | Up to 1 year | 
| Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable) | number of participants responded (complete response, partial response, stable disease, progressive disease, not evaluable) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) | Up to 1 year |