Clinical trial NCT02454842: Study for Treatment With TH-4000 (Tarloxotinib) in Epidermal Growth Factor Receptor (EGFR) Mutant, T790M-negative Non-small Cell Lung Cancer (NSCLC) Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
NSCLC
Non-squamous NSCLC
Keywords: TH-4000
low-oxygen conditions
hypoxia
non-small cell lung cancer
NSCLC
squamous cell carcinoma
Tarloxotinib
Lead sponsor: Rain Oncology Inc
Sponsor class: INDUSTRY
First posted: 2015-05-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Number of participants with response rate as evaluated by RECIST criteria
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Type of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Severity of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Duration of response (DOR) calculated for all patients achieving an objective response
timeFrame: Approximately 12 months
measure: Progression-free survival (PFS)
timeFrame: Approximately 12 months
measure: Overall Survival (OS)
timeFrame: Approximately 12 months
measure: Time to peak plasma concentration (Tmax)
timeFrame: Cycle 1 Day 1 predose and up to 24 hours post dose
measure: Maximum plasma concentration (Cmax)
timeFrame: Cycle 1 Day 1 predose and up to 24 hours post dose
measure: Area under concentration-time curve (AUC)
timeFrame: Cycle 1 Day 1 predose and up to 24 hours post dose
measure: QTc Interval
timeFrame: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles
Other outcomes:
measure: Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging
timeFrame: Baseline
Locations:
city: Los Angeles
country: United States
facility: University of Southern California-Norris
state: California
city: Santa Rosa
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania-Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center (VICC)
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Melbourne
country: Australia
facility: Peter MacCullum
state: Victoria
Study officials:
affiliation: Georgetown University Hospital Cancer Center
name: Stephen Liu
role: PRINCIPAL_INVESTIGATOR
References: