Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens
Condition: Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage III Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: nintedanib
Intervention description: Given PO
Intervention MeSH terms: Nintedanib; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nintedanib works in treating patients with advanced
      non-small cell lung cancer who have failed up to two previous chemotherapy regimens.
      Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with advanced histologically proven squamous cell carcinoma of the lung

          -  Patients who have failed at least 1 systemic chemotherapy regimen for metastatic
             disease, but not more than 2 regimens

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1

          -  The pathologic tissue is available to determine FGFR1 amplification status

          -  Presence of either evaluable disease or measurable disease as defined by Response
             Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Hemoglobin (HgB) >= 9 g/dL

          -  Platelets >= 100,000/uL

          -  Total bilirubin =< upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x ULN (ALT
             and AST =< 2.5 x ULN is acceptable if there is liver metastasis)

          -  Calculated or measured creatinine clearance >= 45 mL/min

          -  Patients of child-bearing potential must agree to use acceptable contraceptive methods
             (e.g., double barrier) during treatment and have a negative serum or urine pregnancy
             test done =< 7 days prior to registration (for women of childbearing potential only)

          -  Life expectancy >= 12 weeks

          -  Willingness to provide the blood specimens as required by the protocol; please note
             that the willingness to participate pertains only to the patient and does not factor
             in the institution's ability to participate in any part of the translational component

        Exclusion Criteria:

          -  Patients with any known endothelial growth factor receptor (EGFR) mutation and/or
             anaplastic lymphoma receptor tyrosine kinase (ALK) translocation

          -  Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or
             seizure disorder; patients with asymptomatic CNS metastases treated with whole brain
             radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after
             completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade
             I at the time of registration and/or controlled with dexamethasone 2 mg once daily for
             at least 5 days at the time of study treatment; patients with symptomatic CNS
             metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of
             WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and
             neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1
             week at the time of study treatment

          -  Patients receiving palliative radiation to skeletal metastases may be registered as
             early as 1 week after completion of radiation therapy provided toxicities are =< CTC
             grade I at the time of registration

          -  Any of the following prior therapies for malignancy:

               -  Systemic chemotherapy =< 4 weeks prior to registration

               -  Radiation therapy =< 4 weeks prior to registration (exceptions noted in the prior
                  bullet); the site of previous radiotherapy should have evidence of progressive
                  disease if this is the only site of disease

               -  Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =<
                  4 weeks prior to registration; minor surgery =< 2 weeks prior to registration;
                  insertion of a vascular access device is not considered major or minor surgery in
                  this regard

               -  Other investigational agent =< 30 days prior to study treatment

          -  The following patients will be excluded from this study:

               -  Pregnant women

               -  Breastfeeding women

               -  Men or women who are sexually active and unwilling to use a medically acceptable
                  method of contraception (e.g., such as implants, injectables, combined oral
                  contraceptives, some intrauterine devices or vasectomized partner for
                  participating females, condoms for participating males) during the trial and for
                  at least three months after end of active therapy; a highly effective method of
                  birth control is defined as one which results in a low failure rate (i.e., less
                  than 1% per year) when used consistently and correctly; patients will be
                  considered to be of childbearing potential unless surgically sterilized by
                  hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at
                  least 2 years

          -  Second primary malignancy with the following exceptions which are allowed:

               -  Carcinoma in situ of the cervix

               -  Non-melanoma skin cancer

               -  History of low-grade (Gleason score =< 6) localized prostate cancer even if
                  diagnosed < 5 years prior to registration

               -  Treated stage I breast cancer even if diagnosed =< 5 years prior to registration

               -  Other prior malignancy (including melanoma) allowed if it was diagnosed and
                  definitively treated at least 5 years previously with no subsequent evidence of
                  recurrence

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of BIBF 1120 (e.g., ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or extensive small
             bowel resection)

          -  Leptomeningeal disease

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy are excluded because of possible pharmacokinetic interactions
             with oral investigational agents

          -  Unwilling to, or unable to, comply with the protocol

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection requiring systemic antimicrobial therapy (including history of active or
             chronic hepatitis C and/or hepatitis B infection), significant pulmonary symptoms at
             baseline due to disease, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Centrally located tumors with radiographic evidence (computed tomography [CT] or
             magnetic resonance imaging [MRI]) of local invasion of major blood vessels

          -  Significant weight loss (> 10% of baseline body mass) within past 6 months prior to
             inclusion into the study

          -  Coagulation parameters: International normalized ratio (INR) > 2, prothrombin time
             (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN

          -  Proteinuria by Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or
             greater

          -  Known inherited predisposition to bleeding or thrombosis

          -  Therapeutic anticoagulation (except for 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 < 325 mg per day)

          -  Baseline hemoptysis, per clinician/investigator evaluation

          -  Active alcohol or drug abuse

          -  History of arterial or venous thrombotic/embolic events =< 12 months prior to
             registration

          -  Prior history with BIBF 1120 or any other vascular endothelial growth factor
             (VEGF)/VEGF receptor (R) inhibitor

          -  New York Heart Association (NYHA) class III or IV; NOTE: patients classified as NYHA
             class II controlled with treatment may participate, with increased monitoring