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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02454842




Registration number
NCT02454842
Ethics application status
Date submitted
4/05/2015
Date registered
27/05/2015
Date last updated
27/02/2017

Titles & IDs
Public title
Study for Treatment of Patients With EGFR Mutant, T790M-negative NSCLC
Scientific 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
Secondary ID [1] 0 0
TH-CR-601
Universal Trial Number (UTN)
Trial acronym
TH-4000
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
NSCLC 0 0
Non-squamous NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TH-4000 (Tarloxotinib)

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


Treatment: Drugs: TH-4000 (Tarloxotinib)
TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with response rate as evaluated by RECIST criteria
Timepoint [1] 0 0
Approximately 12 months
Secondary outcome [1] 0 0
Incidence of adverse events (AEs)
Timepoint [1] 0 0
Up to 30 days after last dose
Secondary outcome [2] 0 0
Type of adverse events (AEs)
Timepoint [2] 0 0
Up to 30 days after last dose
Secondary outcome [3] 0 0
Severity of adverse events (AEs)
Timepoint [3] 0 0
Up to 30 days after last dose
Secondary outcome [4] 0 0
Duration of response (DOR) calculated for all patients achieving an objective response
Timepoint [4] 0 0
Approximately 12 months
Secondary outcome [5] 0 0
Progression-free survival (PFS)
Timepoint [5] 0 0
Approximately 12 months
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Approximately 12 months
Secondary outcome [7] 0 0
Time to peak plasma concentration (Tmax) - Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC)
Timepoint [7] 0 0
Cycle 1 Day 1 predose and up to 24 hours post dose
Secondary outcome [8] 0 0
Maximum plasma concentration (Cmax)
Timepoint [8] 0 0
Cycle 1 Day 1 predose and up to 24 hours post dose
Secondary outcome [9] 0 0
Area under concentration-time curve (AUC)
Timepoint [9] 0 0
Cycle 1 Day 1 predose and up to 24 hours post dose
Secondary outcome [10] 0 0
QTc Interval
Timepoint [10] 0 0
Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCullum - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Threshold Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/show/NCT02454842
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stephen Liu
Address 0 0
Georgetown University Hospital Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02454842