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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Head-and-neck Squamous-cell Carcinoma
• Intervention / Treatment: Drug: TH-4000 (Tarloxotinib)

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California-Norris
    • Stanford, California, United States, 94305
      • Stanford School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center (VICC)
  • Texas
    • Dallas, Texas, United States, 75390
      • UT southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: TH-4000 (Tarloxotinib); Other Names: Tarloxotinib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging	Baseline

Collaborators and Investigators

• Sponsor: Rain Oncology Inc
• Investigators: Principal Investigator: Stephen Liu, Georgetown University Hospital Cancer Center

Publications and helpful links

General Publications

• McLean LS, Morris TA, Gramza A, Liu S, Khan SA, Colevas AD, Pearce T, Rischin D. A phase II study of tarloxotinib (a hypoxia activated prodrug of a pan-erb tyrosine kinase inhibitor) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or skin. Invest New Drugs. 2022 Aug;40(4):782-788. doi: 10.1007/s10637-022-01230-w. Epub 2022 Apr 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: May 15, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: skin; Hypoxia; squamous cell carcinoma; TH-4000; Tarloxotinib; the head and neck
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: TH-CR-602