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

Phase 2

Terminated

• Conditions: Metastatic Head-and-neck Squamous-cell Carcinoma
• Interventions: Drug: TH-4000 (Tarloxotinib)

• Registration Number: NCT02449681
• Lead Sponsor: Rain Oncology Inc

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-05-12
• Study First Submitted QC: 2015-05-15
• Study First Posted: 2015-05-20
• Study Start: 2015-08
• Primary Completion: 2017-01
• Study Completion: 2017-01-31
• Disposition First Submitted: 2022-12-08
• Status Verified: 2023-01
• Disposition First Submitted QC: 2023-01-09
• Last Update Submitted: 2023-01-09
• Disposition First Posted: 2023-01-12
• Last Update Posted: 2023-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TH-4000 (Tarloxotinib)	TH-4000 (Tarloxotinib)	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with response rate as evaluated by RECIST criteria	Approximately 12 months

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Approximately 12 months
QTc Interval	Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination
Incidence 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
Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector)	Cycle 1 Day 1 predose and up to 24 hours postdose
Type of adverse events (AEs)	Up to 30 days after last dose
Overall Survival (OS)	Approximately 12 months
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

Trial Locations

Locations (10)

University of Southern California-Norris; 🇺🇸 Los Angeles, California, United States

Walter Reed National Military Cancer Center; 🇺🇸 Bethesda, Maryland, United States

Vanderbilt-Ingram Cancer Center (VICC); 🇺🇸 Nashville, Tennessee, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

Peter MacCallum; 🇦🇺 East Melbourne, Victoria, Australia

Stanford school of Medicine; 🇺🇸 Stanford, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Georgetown Medical Center; 🇺🇸 Washington, District of Columbia, United States