Clinical Trials /

Study for Treatment of Patients With EGFR Mutant, T790M-negative NSCLC

NCT02454842

Description:

This phase 2 study is designed to evaluate the safety and activity of TH-4000 (Tarloxotinib), a hypoxia-activated prodrug, in patients with EGFR-Mutant, T790M-Negative, Advanced non-small cell lung cancer (NSCLC).

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

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Study for Treatment of Patients With <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-keyword">Mutant</span>, T790M-negative <span class="go-doc-concept go-doc-disease">NSCLC</span>

Title

  • Brief Title: Study for Treatment of Patients With EGFR Mutant, T790M-negative NSCLC
  • Official Title: A Phase 2 Study of TH-4000 in Patients With EGFR-Mutant, T790M-Negative, Advanced Non-Small Cell Lung Cancer Progressing on an EGFR Tyrosine Kinase Inhibitor
  • Clinical Trial IDs

    NCT ID: NCT02454842

    ORG ID: TH-CR-601

    Trial Conditions

    Non-small Cell Lung Cancer

    NSCLC

    Non-squamous NSCLC

    Trial Interventions

    Drug Synonyms Arms
    TH-4000 TH-4000

    Trial Purpose

    This phase 2 study is designed to evaluate the safety and activity of TH-4000, a
    hypoxia-activated prodrug, in patients with EGFR-Mutant, T790M-Negative, Advanced non-small
    cell lung cancer (NSCLC).

    Detailed Description

    A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety,
    tolerability and efficacy of TH-4000 will be assessed in patients with EGFR mutant, T790M
    negative advanced NSCLC. Patients must have demonstrated progression during EGFR TKI
    therapy.

    Hypoxia PET scans will be obtained in select centers to analyze potential predictors of
    tumor response.

    Trial Arms

    Name Type Description Interventions
    TH-4000 Experimental TH-4000, 150 mg/m2 will be administered by IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity TH-4000

    Eligibility Criteria

    Key Eligibility Criteria:

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-1

    - Confirmed recurrent Stage IV NSCLC which progressed while on treatment with EGFR TKI

    - Measurable disease according to Response Evaluation Criteria in Solid Tumors version
    1.1 (RECIST 1.1)

    - Documented evidence of an EGFR mutation known to be associated with an EGFR TKI
    sensitivity

    - No history of exon 20 T790M mutation or small cell transformation including an
    assessment from tumor biopsy obtained while on the most recent EGFR TKI therapy

    - No intervening systemic therapy between the end of EGFR TKI treatment and dosing with
    study drug

    - Acceptable laboratory results as indicated by protocol

    - Acceptable cardiac function as indicated by protocol

    Key Exclusion Criteria:

    - Receiving medication that prolongs QT interval, with a risk of causing Torsades de
    Pointes (TdP) unless ECG meets inclusion criteria while on a stable dose of the
    medication

    - Family history of long QTc syndrome

    - Any prior T790M mutation

    - Symptomatic central nervous system (CNS) lesions, or CNS lesions that require therapy

    - Radiation therapy within 2 weeks prior to the first dose of study medication

    - Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose
    of study medication

    - Concurrent active malignancy requiring systemic treatment

    - Any other serious uncontrolled medical disorders or psychological conditions that may
    interfere with study conduct including but not limited to: clinically significant
    active infection

    - Pregnant or breast-feeding

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of participants with response rate as evaluated by RECIST criteria

    Secondary Outcome Measures

    Incidence of adverse events (AEs)

    Type of adverse events (AEs)

    Severity of adverse events (AEs)

    Duration of response (DOR) calculated for all patients achieving an objective response

    Progression-free survival (PFS)

    Overall Survival (OS)

    Time to peak plasma concentration (Tmax)

    Maximum plasma concentration (Cmax)

    Area under concentration-time curve (AUC)

    QTc Interval

    Trial Keywords

    TH-4000

    low-oxygen conditions

    hypoxia

    non-small cell lung cancer

    NSCLC

    squamous cell carcinoma