Clinical Trials /

Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)

NCT02206763

Description:

This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung cancer (NSCLC). Participants will be sequentially enrolled to receive progressively increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will consist of 28 days.

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

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Erlotinib</span> and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (<span class="go-doc-concept go-doc-biomarker">EGFR</span>) <span class="go-doc-concept go-doc-keyword">Mutated</span> <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-intervention">Tyrosine Kinase Inhibitor</span> (<span class="go-doc-concept go-doc-intervention">TKI</span>) Naive Metastatic Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (NSCLC)

Title

  • Brief Title: Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Nave Metastatic Non-Small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02206763

    ORG ID: GS-US-370-1298

    Trial Conditions

    EGFR Mutated EGFR TKI Nave Metastatic NSCLC

    Trial Interventions

    Drug Synonyms Arms
    MMB GS-0387, CYT387 Dose Escalation Phase, MMB+erlotinib, Dose Expansion Phase, MMB+erlotinib
    Erlotinib Dose Escalation Phase, MMB+erlotinib, Dose Expansion Phase, MMB+erlotinib, Dose Expansion Phase, erlotinib

    Trial Purpose

    There will be two parts to this study. The dose escalation phase will evaluate the safety,
    preliminary efficacy, and pharmacokinetics (PK) of momelotinib (MMB) and erlotinib, as well
    as define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with erlotinib in
    adults with epidermal growth factor receptor (EGFR)-mutated, EGFR tyrosine kinase inhibitor
    (TKI) naive metastatic non-small cell lung cancer (NSCLC). During this phase, participants
    will be sequentially enrolled to receive progressively increasing doses of MMB in
    combination with erlotinib. Escalation of MMB doses will proceed to the MTD, defined as the
    highest tested dose associated with dose-limiting toxicities (DLT) during the first 28 days
    of combined erlotinib and MMB treatment. There will be four dose levels and each treatment
    cycle will consist of 28 days.

    The dose expansion phase will evaluate the efficacy, safety, and tolerability of erlotinib
    combined with MMB administered at the MTD versus erlotinib alone in adults with EGFR-Mutated
    EGFR TKI naive metastatic NSCLC.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Dose Escalation Phase, MMB+erlotinib Experimental Participants will receive MMB and erlotinib. MMB, Erlotinib
    Dose Expansion Phase, MMB+erlotinib Experimental Participants will receive MMB and erlotinib. MMB, Erlotinib
    Dose Expansion Phase, erlotinib Experimental Participants will receive erlotinib alone. Erlotinib

    Eligibility Criteria

    Inclusion Criteria:

    - Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R)
    substitution mutation

    - Treatment naive OR one prior standard chemotherapy that is platinum-based

    - Adequate organ function defined as follows:

    - Hepatic: Total bilirubin < upper limit of the normal range (ULN); aspartate
    transaminase (AST) and alanine transaminase (ALT) 3 x ULN

    - Hematological: absolute neutrophil count (ANC) 1500 cells/mm^3, platelet
    100,000 cells/mm^3, hemoglobin 9.0 g/dL

    - Renal: Serum creatinine < ULN OR calculated creatinine clearance (CrCl) of 60
    ml/min

    - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

    Exclusion Criteria:

    - Known positive status for human immunodeficiency virus (HIV)

    - Chronic active or acute viral hepatitis A, B, or C infection (testing required for
    hepatitis B and C)

    - Presence of > Grade 1 peripheral neuropathy

    - Symptomatic leptomeningeal, brain metastases, or spinal cord compression.

    - History of interstitial pneumonitis

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    During the dose escalation phase, incidence of dose limiting toxicities (DLTs)

    During the dose expansion phase, progression free survival

    Secondary Outcome Measures

    During the dose escalation phase, progression free survival

    During the dose escalation phase, overall survival

    During the dose escalation phase, overall response rate

    During the dose escalation phase, PK profile of MMB

    During the dose escalation phase, PK profile of erlotinib

    During the dose expansion phase, overall survival

    During the dose expansion phase, overall response rate

    During the dose expansion phase, PK profile of MMB trough as measured by standardized PK methodology

    Trial Keywords