Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy
Condition: 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
MeSH terms: Pneumonia; Carcinoma; Carcinoma, Non-Small-Cell Lung; Radiation Pneumonitis
Intervention: Durvalumab; Nintedanib; Placebo; Quality-of-Life Assessment
Intervention description: Given IV; Given PO; Given PO; Ancillary studies
Intervention MeSH terms: Durvalumab; Nintedanib; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial studies the side effects and how well nintedanib works compared to a placebo in
      treating against radiation-induced pneumonitis (inflammation of the lungs) in patients with
      non-small cell lung cancer that cannot be removed by surgery and are undergoing
      chemoradiation therapy. Nintedanib may help shrink or slow the growth of radiation-induced
      pneumonitis by blocking some of the enzymes needed for cells to grow and may prevent the
      growth of new blood vessels. It may also help reduce the recurrence of non-small cell lung
      cancer.
    

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