Nintedanib in Treating Patients With Malignant Pleural Mesothelioma That Is Recurrent

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.

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