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Study for Treatment of Patients With EGFR Mutant, T790M-negative NSCLC (TH-4000)

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ClinicalTrials.gov Identifier: NCT02454842
Recruitment Status : Terminated (Lack of efficacy)
First Posted : May 27, 2015
Last Update Posted : February 27, 2017
Information provided by (Responsible Party):
Threshold Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer NSCLC Non-squamous NSCLC Drug: TH-4000 (Tarloxotinib) Phase 2

Detailed Description:

A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 (Tarloxotinib) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2015
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 31, 2017

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Number of participants with response rate as evaluated by RECIST criteria [ Time Frame: Approximately 12 months ]

Secondary Outcome Measures :
  1. Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after last dose ]
  2. Type of adverse events (AEs) [ Time Frame: Up to 30 days after last dose ]
  3. Severity of adverse events (AEs) [ Time Frame: Up to 30 days after last dose ]
  4. Duration of response (DOR) calculated for all patients achieving an objective response [ Time Frame: Approximately 12 months ]
  5. Progression-free survival (PFS) [ Time Frame: Approximately 12 months ]
  6. Overall Survival (OS) [ Time Frame: Approximately 12 months ]
  7. Time to peak plasma concentration (Tmax) [ Time Frame: Cycle 1 Day 1 predose and up to 24 hours post dose ]
    Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC)

  8. Maximum plasma concentration (Cmax) [ Time Frame: Cycle 1 Day 1 predose and up to 24 hours post dose ]
  9. Area under concentration-time curve (AUC) [ Time Frame: Cycle 1 Day 1 predose and up to 24 hours post dose ]
  10. QTc Interval [ Time Frame: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles ]

Other Outcome Measures:
  1. Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging [ Time Frame: Baseline ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02454842

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United States, California
University of Southern California-Norris
Los Angeles, California, United States, 90033
St. Joseph Heritage Healthcare
Santa Rosa, California, United States, 95403
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Maryland
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889
United States, North Carolina
University of North Carolina Lineberger Cancer Center
Chapel Hill, North Carolina, United States, 27514
United States, Pennsylvania
University of Pennsylvania-Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt-Ingram Cancer Center (VICC)
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75235
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Australia, Victoria
Peter MacCullum
Melbourne, Victoria, Australia, 3002
Sponsors and Collaborators
Threshold Pharmaceuticals
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Principal Investigator: Stephen Liu Georgetown University Hospital Cancer Center
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Responsible Party: Threshold Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02454842    
Other Study ID Numbers: TH-CR-601
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: February 27, 2017
Last Verified: June 2016
Keywords provided by Threshold Pharmaceuticals:
low-oxygen conditions
non-small cell lung cancer
squamous cell carcinoma
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms