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

Non-small Cell Lung Cancer Clinical Trial

— TH-4000  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02454842
• Other study ID #: TH-CR-601
• Status: Terminated
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: January 31, 2017

Study information

• Verified date: January 2023
• Source: Rain Oncology Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: January 31, 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Non-squamous NSCLC
• NSCLC

Intervention

Drug:
• TH-4000 (Tarloxotinib)
TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug

Locations

Country	Name	City	State
Australia	Peter MacCullum	Melbourne	Victoria
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of North Carolina Lineberger Cancer Center	Chapel Hill	North Carolina
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Southern California-Norris	Los Angeles	California
United States	Vanderbilt-Ingram Cancer Center (VICC)	Nashville	Tennessee
United States	University of Pennsylvania-Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Rain Oncology Inc

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging		Baseline
Primary	Number of participants with response rate as evaluated by RECIST criteria		Approximately 12 months
Secondary	Incidence of adverse events (AEs)		Up to 30 days after last dose
Secondary	Type of adverse events (AEs)		Up to 30 days after last dose
Secondary	Severity of adverse events (AEs)		Up to 30 days after last dose
Secondary	Duration of response (DOR) calculated for all patients achieving an objective response		Approximately 12 months
Secondary	Progression-free survival (PFS)		Approximately 12 months
Secondary	Overall Survival (OS)		Approximately 12 months
Secondary	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
Secondary	Maximum plasma concentration (Cmax)		Cycle 1 Day 1 predose and up to 24 hours post dose
Secondary	Area under concentration-time curve (AUC)		Cycle 1 Day 1 predose and up to 24 hours post dose
Secondary	QTc Interval		Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles