Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin

Study Overview
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Brief Summary
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This phase 2 study is designed to evaluate the safety and activity of TH-4000, a hypoxia-activated prodrug in participants with recurrent or metastatic squamous cell carcinoma of the head and neck or skin.

Detailed Description
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An open label, multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 will be assessed in participants with recurrent or metastatic squamous cell carcinoma of the head and neck or skin. Hypoxia PET scans will be obtained in select centers to analyze potential predictors of tumor response.

Official Title
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A Phase 2 Study of Tarloxotinib (TH-4000) in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin

Conditions
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Metastatic Head-and-neck Squamous-cell Carcinoma

Intervention / Treatment
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* Drug: TH-4000 (Tarloxotinib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Confirmed squamous cell carcinoma (SCC) of the head and neck (oropharynx, oral cavity, hypopharynx, or larynx) or skin For patients with oropharyngeal cancer, p16 status is known or can be determined Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Acceptable laboratory results as indicated by protocol Acceptable cardiac function as indicated by protocol Exclusion Criteria: Received prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for recurrent or metastatic Squamous Cell Carcinoma (e.g., oral EGFR TKIs such as erlotinib, gefitinib, or afatinib) Family history of long corrected QT interval (QTc) syndrome 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, or CNS lesions that require therapy 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 Pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label single arm two-stage, phase-2 study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TH-4000 (Tarloxotinib)<br>TH-4000 150 mg/m2 will be administered by IV infusion over 60 minutes on Days 1, 8, 15 and 22 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity. | Drug: TH-4000 (Tarloxotinib)<br> <br> * Other names: Tarloxotinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with response rate as evaluated by RECIST criteria |  | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 30 days after last dose | 
| Type of adverse events (AEs) |  | Up to 30 days after last dose | 
| Severity of adverse events (AEs) |  | Up to 30 days after last dose | 
| Duration of response (DOR) calculated for all patients achieving an objective response |  | Approximately 12 months | 
| Progression-free survival (PFS) |  | Approximately 12 months | 
| Overall Survival (OS) |  | Approximately 12 months | 
| Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector) |  | Cycle 1 Day 1 predose and up to 24 hours postdose | 
| Area under the plasma concentration versus time curve of TH4000 (prodrug) and TH-4000E (TKI effector) |  | Cycle 1 Day 1 predose and up to 24 hours postdose | 
| QTc Interval |  | Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin, squamous cell carcinoma, the head and neck, TH-4000, Hypoxia, Tarloxotinib