Clinical Trials /

Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens

NCT01948141

Description:

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.

Related Conditions:
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Nintedanib</span> in Treating Patients With Advanced Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> Who Have Failed Up to Two Previous <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> Regimens

Title

  • Brief Title: Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens
  • Official Title: FGFR1 Amplification as A Predictor of Efficacy in A Biomarker-Driven Phase II Study of BIBF 1120 in Advanced Squamous Cell Lung Cancer Patients Who Have Failed Up to Two Prior Chemotherapeutic Regimens
  • Clinical Trial IDs

    NCT ID: NCT01948141

    ORG ID: I 225512

    NCI ID: NCI-2013-01618

    Trial Conditions

    Recurrent Non-small Cell Lung Cancer

    Squamous Cell Lung Cancer

    Stage III Non-small Cell Lung Cancer

    Stage IV Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    nintedanib BIBF 1120, multitargeted tyrosine kinase inhibitor BIBF 1120, Tyrosine Kinase Inhibitor BIBF 1120, Vargatef Treatment (nintedanib)

    Trial Purpose

    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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate the 6-month progression-free survival (PFS) rate of fibroblast growth factor
    receptor 1 (FGFRI) amplified squamous cell lung cancer patients treated with BIBF 1120
    (nintedanib).

    SECONDARY OBJECTIVES:

    I. Compare the 6-month PFS rate for the entire FGFRI amplified group versus the FGFRI
    wild-type patients.

    II. Compare the 6-month PFS rate for each FGFRI amplified group (low, intermediate, and
    high) versus historical controls and FGFRI wild-type patients.

    III. To assess the following endpoints overall and by FGFRI group: PFS, overall survival
    (OS), confirmed tumor response rate, and adverse events.

    TERTIARY OBJECTIVES:

    I. The relation of FGFRI gene copy number with PFS, OS, confirmed response rate, and adverse
    events.

    II. The relationship fibroblast growth factor receptor (FGFR) polymorphisms with toxicity
    and efficacy.

    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 every 8 weeks.

    Trial Arms

    Name Type Description Interventions
    Treatment (nintedanib) Experimental Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. nintedanib

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS rate within the entire FGFRI amplified group defined as the proportion of patients who are alive and progression-free

    Secondary Outcome Measures

    PFS rate for the entire FGFR1 amplified group vs. the FGFRI wild-type patients

    PFS rate between each of the FGFR1 amplified groups (low, intermediate, and high) vs. the FGFR1 wild-type patients

    PFS rate for each of the FGFRI amplified groups (low, intermediate, high) in comparison to historical controls

    OS

    Tumor response defined as complete response (CR) or partial response by RECIST 1.1 criteria

    Incidence of adverse events (AEs) accessed by the National Cancer Institute (NCI) CTCAE version 4.0

    Trial Keywords