Study for Treatment With TH-4000 (Tarloxotinib) in Epidermal Growth Factor Receptor (EGFR) Mutant, T790M-negative Non-small Cell Lung Cancer (NSCLC) Patients

Phase 2

Terminated

• Conditions: Non-small Cell Lung Cancer; NSCLC; Non-squamous NSCLC
• Interventions: Drug: TH-4000 (Tarloxotinib)

• Registration Number: NCT02454842
• Lead Sponsor: Rain Oncology Inc

Brief Summary

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 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.

Study Timeline

• Study First Submitted: 2015-05-04
• Study First Submitted QC: 2015-05-21
• Study First Posted: 2015-05-27
• Study Start: 2015-06
• Primary Completion: 2017-01
• Study Completion: 2017-01-31
• Disposition First Submitted: 2022-12-07
• Disposition First Submitted QC: 2022-12-07
• Disposition First Posted: 2022-12-12
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-09
• Last Update Posted: 2023-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

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 corrected QT interval (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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TH-4000 (Tarloxotinib)	TH-4000 (Tarloxotinib)	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

Primary Outcome Measures

Name	Time	Method
Number of participants with response rate as evaluated by RECIST criteria	Approximately 12 months

Secondary Outcome Measures

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

Trial Locations

Locations (12)

St. Joseph Heritage Healthcare; 🇺🇸 Santa Rosa, California, United States

University of North Carolina Lineberger Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

Peter MacCullum; 🇦🇺 Melbourne, Victoria, Australia

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of Southern California-Norris; 🇺🇸 Los Angeles, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Walter Reed National Military Medical Center; 🇺🇸 Bethesda, Maryland, United States

University of Pennsylvania-Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt-Ingram Cancer Center (VICC); 🇺🇸 Nashville, Tennessee, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States