Clinical trial NCT02452463 (phase 2, status: terminated)
Conditions: lung non-squamous non-small cell carcinoma, radiation-induced pneumonitis, stage ii lung non-small cell cancer ajcc v7, stage iia lung non-small cell carcinoma ajcc v7, stage iib lung non-small cell carcinoma ajcc v7, stage iii lung non-small cell cancer ajcc v7, stage iiia lung non-small cell cancer ajcc v7, stage iiib lung non-small cell cancer ajcc v7, stage iv lung non-small cell cancer ajcc v7
ICD codes: D02.20, D02.21, D02.22, G62.82, C96.20, C96.29, D47.09, D02.20, D02.21, D02.22, D02.20, D02.21, D02.22, C96.20, C96.29, D47.09, C96.20, C96.29, D47.09, C96.20, C96.29, D47.09, C96.20, C96.29, D47.09
Drugs: nintedanib
SMILES: COC(=O)C1=CC=C2C(NC(=O)\C2=C(/NC2=CC=C(C=C2)N(C)C(=O)CN2CCN(C)CC2)C2=CC=CC=C2)=C1
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically-proven non squamous cell NSCLC; mixed histology with
             small cell lung carcinoma (SCLC) component not allowed

          -  Patients with stage II ? IV non squamous cell NSCLC who received at least 54 Gy of
             total planned thoracic radiation dose will be eligible; patients must have received at
             least one cycle of chemotherapy concurrently during the course of thoracic radiation;
             regimens allowed are platinum combinations with either etoposide or a taxane
             regardless of histology subtype; platinum with pemetrexed for patients with
             non-squamous NSCLC only; patients with oligometastatic stage IV cancer are eligible if
             they have received only one line of systemic therapy for their stage IV cancer prior
             to the concurrent chemoradiation phase

          -  Patient must have had a complete response (CR)/partial response (PR)/stable disease
             (SD), 4-6 weeks after completing last fraction of radiation therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0-2

          -  Absolute neutrophil count (ANC) >= 1,500/uL

          -  Platelet count >= 100,000/uL

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< normal or for those with Gilbert?s syndrome =< 1.5 times upper
             limit of normal (ULN) OR direct bilirubin normal (per institute standards)

          -  Aspartate aminotransferase (AST) =< 1.5 x ULN; alanine aminotransferase (ALT) and AST
             =< 2.5 x ULN is acceptable if there is liver metastasis

          -  Fertile patients must use adequate contraception

        Exclusion Criteria:

          -  Whole-brain radiotherapy (WBRT) < 14 days from the anticipated start of
             nintedanib/placebo administration

          -  Squamous cell NSCLC

          -  Unable to start nintedanib/placebo treatment between 4-8 weeks after completing the
             last dose of thoracic radiation

          -  Active untreated brain or leptomeningeal metastases; in patients with treated central
             nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks;
             dexamethasone allowed if total daily dose does not exceed 2 mg

          -  Major injuries or surgery (e.g., craniotomy) < 28 days from the start of
             nintedanib/placebo administration; wound should be healed prior to starting therapy

          -  Second malignancies are allowed as long as the disease does not require active
             treatment with concomitant systemic cytotoxic chemotherapy, investigational or
             biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] or
             human epidermal growth factor receptor 2 [HER2] monoclonal antibodies);
             hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists,
             tamoxifen, etc.) are allowed

          -  Concurrent uncontrolled illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situation that would increase the risk
             associated with study participation and/or limit compliance with study requirements

          -  Inability to swallow study medication

          -  Presence of active malabsorption disorder (e.g., flare episodes documented within the
             preceding 3 months, presence of symptoms requiring daily medications for control) or
             history of extensive small bowel resection

          -  Known bleeding or thrombotic diathesis

          -  History of arterial or venous thromboembolic event within 12 months prior to study
             participation

          -  Active hemoptysis or history of clinically relevant hemoptysis as determined by the
             treating physician; patients who had history of transient minor hemoptysis after
             bronchoscopic biopsy are eligible unless deemed otherwise by the treating physician

          -  Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher proteinuria

          -  Investigational agent administered < 28 days prior to treatment with nintedanib. Last
             dose of systemic chemotherapy administered < 14 days prior to treatment with
             nintedanib

          -  Known chronic active hepatitis B or hepatitis C; human immunodeficiency virus
             (HIV)-positive patients receiving or are candidates for antiretroviral therapy are
             also excluded

          -  Pregnancy or breast feeding; female patients with child-bearing potential must have a
             negative pregnancy test (beta-human chorionic gonadotropin [B-HCG] test in urine or
             serum) prior to commencing study treatment

          -  Creatinine > 1.5 x ULN or creatinine clearance levels (CrCL) < 45 mL/min

          -  Centrally located tumors with radiographic evidence (computed tomography [CT] or
             magnetic resonance imaging [MRI]) of local invasion of major blood vessels

          -  Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed
             for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except
             for low-dose therapy with acetylsalicylic acid < 325 mg per day)

          -  Active or previous autoimmune disease requiring treatment within the past 2 years will
             exclude patients from receiving immune checkpoint inhibitor in this study. Exception
             allowed: endocrine conditions treated with necessary hormone replacement or other
             supportive medication; vitiligo, alopecia