Overview

This trial is active, not recruiting.

Conditions non-small cell lung cancer, nsclc, non-squamous nsclc
Treatment th-4000 (tarloxotinib)
Phase phase 2
Targets EGFR, HER2
Sponsor Threshold Pharmaceuticals
Start date June 2015
End date December 2016
Trial size 37 participants
Trial identifier NCT02454842, TH-CR-601

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
TH-4000 (Tarloxotinib), 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 (tarloxotinib)
TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug

Primary Outcomes

Measure
Number of participants with response rate as evaluated by RECIST criteria
time frame: Approximately 12 months

Secondary Outcomes

Measure
Incidence of adverse events (AEs)
time frame: Up to 30 days after last dose
Type of adverse events (AEs)
time frame: Up to 30 days after last dose
Severity of adverse events (AEs)
time frame: Up to 30 days after last dose
Duration of response (DOR) calculated for all patients achieving an objective response
time frame: Approximately 12 months
Progression-free survival (PFS)
time frame: Approximately 12 months
Overall Survival (OS)
time frame: Approximately 12 months
Time to peak plasma concentration (Tmax)
time frame: Cycle 1 Day 1 predose and up to 24 hours post dose
Maximum plasma concentration (Cmax)
time frame: Cycle 1 Day 1 predose and up to 24 hours post dose
Area under concentration-time curve (AUC)
time frame: Cycle 1 Day 1 predose and up to 24 hours post dose
QTc Interval
time frame: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles

Eligibility Criteria

Male or female participants at least 18 years old.

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 T790M mutation or small cell transformation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy - 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 - Symptomatic central nervous system (CNS) lesions - 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 (e.g., tuberculosis, viral hepatitis, human immunodeficiency virus [HIV]), recent (within 6 months) myocardial infarction or unstable angina, congestive heart failure, poorly-controlled hypertension or diabetes, concurrent active malignancy, or psychiatric condition that may interfere with the patient's ability to follow study procedures - Pregnant or breast-feeding

Additional Information

Official title A Phase 2 Study of TH-4000 (Tarloxotinib) in Patients With EGFR-Mutant, T790M-Negative, Advanced Non-Small Cell Lung Cancer Progressing on an EGFR Tyrosine Kinase Inhibitor
Principal investigator Stephen Liu
Description A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 (Tarloxotinib) 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 information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Threshold Pharmaceuticals.
Location data was received from the National Cancer Institute and was last updated in June 2016.