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

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

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.

Study Overview

• Status: Terminated
• Conditions: NSCLC; Non-small Cell Lung Cancer; Non-squamous NSCLC
• Intervention / Treatment: Drug: TH-4000 (Tarloxotinib)

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Peter MacCullum
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California-Norris
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Lineberger Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania-Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center (VICC)
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: TH-4000 (Tarloxotinib); TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with response rate as evaluated by RECIST criteria	Approximately 12 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging	Baseline

Collaborators and Investigators

• Sponsor: Rain Oncology Inc
• Investigators: Principal Investigator: Stephen Liu, Georgetown University Hospital Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; hypoxia; squamous cell carcinoma; TH-4000; low-oxygen conditions; Tarloxotinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: TH-CR-601