We encourage participation in clinical trials for research leading to a cure for mesothelioma. It is known that nationally the statistics for participation in adult cancer trials is between 3-5% of adults who have a cancer diagnosis.

For mesothelioma patients and families who are interested in clinical trials, researching clinical trials and eligibility can be a time- consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov

CLINICAL TRIAL– NCT02568449

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

Listing on- www.clinicaltrials.gov

Sponsor- Barbara Ann Karmanos Cancer Institute Wayne State University 4100 John R Detroit, Michigan 48201

Collaborator: National Cancer Institute

Location: 4 total sites- 2 are recruiting 2 not yet recruiting-

• University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan, United States 48109 contact Gregory P. Kalemkerian 734 615 4762 kalemker@umich.edu- recruiting
• Wayne State University/Karmanos Cancer Institute Detroit Michigan, United States 48201 contact Antoinette J. Wozniak 313 576 8752 wozniakt@karmanos.org -recruiting
• University of California Davis Comprehensive Cancer Center Sacramento California, United States 95817 contact David R. Gandara 916 734 8452 david.gandara@ucdmc.ucdavis.edu- not yet recruiting
• Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 contact Marjorie G. Zauderer MD zauderem@mskcc.org – not yet recruiting

Principal Investigator Antoinette J. Wozniak, Barbara Ann Karmanos Cancer Institute Wayne State University 4100 John R Detroit Michigan 48201

Contact– Listed above by site.

Number of Participants– 55 starting date October 2015- estimated completion date January 1, 2018

Purpose- A phase ll trial to study 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.

Eligibility Criteria- Adults over age 18 male or female

Inclusion and Exclusion Criteria:

• Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma
• Patients must have a Ct scan within 28 days of beginning trial to measure disease- all disease must be assessed by the 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
• 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, pleurodesis) provided that at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered
• 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)
• Liver tests- SGOT, AST, SGPT must be less than institution upper limit of normal
• Renal tests- less than IULN obtained within 14 days
• 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 hemorrhagic or thromboembolic event in the past 6 months
• Patients must have no evidence of bleeding 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

How the Research Study is Designed to Work-

PRIMARY OBJECTIVES:

1. To assess the 4-month progression-free survival (PFS) in patients with recurrent, unresectable malignant pleural mesothelioma (MAM) treated with Nintedanib.

SECONDARY OBJECTIVES:

1. 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.
2. To assess overall survival.

III. To evaluate the frequency and severity of toxicities associated with this treatment regimen.

1. To collect tissue samples for future correlative studies related to overall study objectives.

With any clinical trial, all participation is voluntary. Before enrollment a detailed consent form will be reviewed with the participant and signed. The participant can withdraw from a clinical trial at any point in time. Think about participating if able, the only way to progress to a cure for mesothelioma is through clinical trials.

Please do not hesitate to contact us with any questions.