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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)

Primary Purpose

Non-small Cell Lung Cancer, NSCLC, Non-squamous NSCLC

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TH-4000 (Tarloxotinib)
Sponsored by
Rain Oncology Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring TH-4000, low-oxygen conditions, hypoxia, non-small cell lung cancer, NSCLC, squamous cell carcinoma, Tarloxotinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Southern California-Norris
  • St. Joseph Heritage Healthcare
  • University of Colorado Cancer Center
  • Georgetown University Medical Center
  • Walter Reed National Military Medical Center
  • University of North Carolina Lineberger Cancer Center
  • University of Pennsylvania-Abramson Cancer Center
  • University of Pittsburgh Medical Center
  • Vanderbilt-Ingram Cancer Center (VICC)
  • UT Southwestern Medical Center
  • Swedish Cancer Institute
  • Peter MacCullum

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TH-4000 (Tarloxotinib)

Arm Description

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

Outcomes

Primary Outcome Measures

Number of participants with response rate as evaluated by RECIST criteria

Secondary Outcome Measures

Incidence of adverse events (AEs)
Type of adverse events (AEs)
Severity of adverse events (AEs)
Duration of response (DOR) calculated for all patients achieving an objective response
Progression-free survival (PFS)
Overall Survival (OS)
Time to peak plasma concentration (Tmax)
Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC)
Maximum plasma concentration (Cmax)
Area under concentration-time curve (AUC)
QTc Interval

Full Information

First Posted
May 4, 2015
Last Updated
January 9, 2023
Sponsor
Rain Oncology Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02454842
Brief Title
Study for Treatment With TH-4000 (Tarloxotinib) in Epidermal Growth Factor Receptor (EGFR) Mutant, T790M-negative Non-small Cell Lung Cancer (NSCLC) Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
June 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rain Oncology Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TH-4000 (Tarloxotinib)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
TH-4000 (Tarloxotinib)
Intervention Description
TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug
Primary Outcome Measure Information:
Title
Number of participants with response rate as evaluated by RECIST criteria
Time Frame
Approximately 12 months
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Type of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Severity of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Duration of response (DOR) calculated for all patients achieving an objective response
Time Frame
Approximately 12 months
Title
Progression-free survival (PFS)
Time Frame
Approximately 12 months
Title
Overall Survival (OS)
Time Frame
Approximately 12 months
Title
Time to peak plasma concentration (Tmax)
Description
Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC)
Time Frame
Cycle 1 Day 1 predose and up to 24 hours post dose
Title
Maximum plasma concentration (Cmax)
Time Frame
Cycle 1 Day 1 predose and up to 24 hours post dose
Title
Area under concentration-time curve (AUC)
Time Frame
Cycle 1 Day 1 predose and up to 24 hours post dose
Title
QTc Interval
Time Frame
Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles
Other Pre-specified Outcome Measures:
Title
Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Liu
Organizational Affiliation
Georgetown University Hospital Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California-Norris
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
St. Joseph Heritage Healthcare
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Facility Name
University of North Carolina Lineberger Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
University of Pennsylvania-Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center (VICC)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Peter MacCullum
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

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

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