Clinical Trials /

Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)

NCT02705339

Description:

Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. The investigators propose to conduct a clinical trial of rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients, pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Rociletinib</span> <span class="go-doc-concept go-doc-keyword">Genomic</span> Landscape in Non-small Cell Lung Cancer (<span class="go-doc-concept go-doc-disease">NSCLC</span>)

Title

  • Brief Title: Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
  • Official Title: Genomic Landscape of EGFR Mutant NSCLC Prior to Rociletinib and at the Time of Disease Progression Following Rociletinib
  • Clinical Trial IDs

    NCT ID: NCT02705339

    ORG ID: 15-x375

    Trial Conditions

    Carcinoma, Non-Small-Cell Lung

    Non-Small Cell Lung Cancer

    Nonsmall Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Rociletinib CO-1686 Arm 1: Rociletinib

    Trial Purpose

    Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib,
    there is a need to understand the molecular mechanisms that lead to primary and acquired
    resistance to rociletinib. The investigators propose to conduct a clinical trial of
    rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including
    exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients,
    pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to
    fully understand the clonal evolution and the molecular mechanisms underpinning treatment
    resistance.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1: Rociletinib Experimental Rociletinib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg twice per day during each 28-day cycle. After completion of cycle 1, patients who tolerate the 500 mg twice per day dose without significant adverse effect may increase dosing to 625 mg twice per day at the discretion of the investigator Rociletinib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed metastatic stage IIIB/IV lung
    adenocarcinoma with known activating mutations in the EGFR TK domain (including exon
    19 deletion and L858R)

    - Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor
    biopsy; however, this need not be only second line

    - Measurable disease defined as lesions that can be accurately measured in at least one
    dimension (longest diameter to be recorded) as 10 mm with CT scan, as 20 mm by
    chest x-ray, or 10 mm with calipers by clinical exam.

    - At least 18 years of age.

    - ECOG performance status 2

    - Normal bone marrow and organ function as defined below:

    - Leukocytes 3,000/mcL

    - Absolute neutrophil count 1,500/mcl

    - Platelets 100,000/mcl

    - Hemoglobin 9.0 g/dL

    - INR 2.0

    - Total bilirubin 1.5 x IULN

    - AST(SGOT)/ALT(SGPT) 3.0 x IULN

    - Creatinine IULN OR creatinine clearance 45 mL/min/1.73 m2 for patients with
    creatinine levels above institutional normal

    - Potassium within institutional limits (supplementation allowed)

    - Magnesium within normal limits (supplementation allowed)

    - Tumor tissue available and deemed adequate for genomic studies.

    - Women of childbearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control, abstinence) prior to study entry and
    for the duration of study participation. Should a woman become pregnant or suspect
    she is pregnant while participating in this study, she must inform her treating
    physician immediately.

    - Ability to understand and willingness to sign an IRB approved written informed
    consent document (or that of legally authorized representative, if applicable).

    Exclusion Criteria:

    - A history of other malignancy 5 years previous with the exception of basal cell or
    squamous cell carcinoma of the skin which were treated with local resection only or
    carcinoma in situ of the cervix.

    - Currently receiving any other investigational agents.

    - Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of
    study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a
    urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
    eligible.

    - Symptomatic, untreated or unstable central nervous system or leptomeningeal
    metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans
    at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain
    lesion are eligible provided that they are asymptomatic and do not require
    corticosteroids.)

    - A history of allergic reactions attributed to compounds of similar chemical or
    biologic composition to rociletinib or other agents used in the study.

    - Currently receiving treatment with any medication that has the potential to prolong
    the QT interval and the treatment cannot be discontinued or switched to a different
    medication.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
    infarction within the previous 3 months, coronary angioplasty or stenting or bypass
    grafting within the past 6 months, cardiac ventricular arrhythmias requiring
    medication, any history of 2nd or 3rd degree atrioventricular conduction defects,
    cardiac arrhythmia, or psychiatric illness/social situations that would limit
    compliance with study requirements.

    - History of interstitial lung disease.

    - History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
    obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
    pneumonitis on screening chest CT scan. History of radiation pneumonitis in the
    radiation field (fibrosis) is permitted.

    - Class II to IV heart failure as defined by the New York Heart Association functional
    classification system. Patients with known coronary artery disease, congestive heart
    failure not meeting the above criteria, or LVEF < 50% must be on a stable medial
    regimen that is optimized in the opinion of the treating physician, in consultation
    with a cardiologist if appropriate, to be eligible.

    - Any of the following cardiac abnormalities or history:

    - Clinically significant abnormal 12-lead ECG, QT interval corrected using
    Fridericia's method (QTcF) > 450 msec

    - Inability to measure QT interval on ECG

    - Personal or family history of long QT syndrome

    - Implantable pacemaker or implantable cardioverter defibrillator

    - Resting bradycardia < 55 beats/min

    - Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
    pregnancy test within 7 days of study entry.

    - Known HIV-positivity on combination antiretroviral therapy because of the potential
    for pharmacokinetic interactions with rociletinib. In addition, these patients are at
    increased risk of lethal infections when treated with marrow-suppressive therapy.
    Appropriate studies will be undertaken in patients receiving combination
    antiretroviral therapy when indicated.

    - Active hepatitis B virus (HBV) defined by positive hepatitis B surface antigen
    (HBsAg) test at screening. Patients with past or resolved HBV infection (defined by a
    negative HBsAg test and a positive anti-hepatitis B core antigen (anti-HBc) antibody
    test) are eligible. HBV DNA must be obtained in these patients prior to first day of
    study treatment.

    - Active hepatitis C virus (HCV). Patients positive for HCV antibody are eligible only
    if PCR is negative for HCV RNA.

    - Active tuberculosis.

    - Presence of active GI disease (including GI bleeding or ulceration) or other
    condition that could affect GI absorption) (e.g. malabsorption syndrome, history of
    biliary tract disease).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Somatic genetic changes in the tumor associated with disease progression

    Secondary Outcome Measures

    Overall response rate (ORR)

    Overall survival (OS)

    Progression-free survival (PFS)

    Duration of treatment

    Trial Keywords