Clinical trial NCT02449681: Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin
Official title: A Phase 2 Study of Tarloxotinib (TH-4000) in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Head-and-neck Squamous-cell Carcinoma
Keywords: squamous cell carcinoma
the head and neck
skin
TH-4000
Hypoxia
Tarloxotinib
Lead sponsor: Rain Oncology Inc
Sponsor class: INDUSTRY
First posted: 2015-05-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label single arm two-stage, phase-2 study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with response rate as evaluated by RECIST criteria
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Type of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Severity of adverse events (AEs)
timeFrame: Up to 30 days after last dose
measure: Duration of response (DOR) calculated for all patients achieving an objective response
timeFrame: Approximately 12 months
measure: Progression-free survival (PFS)
timeFrame: Approximately 12 months
measure: Overall Survival (OS)
timeFrame: Approximately 12 months
measure: Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector)
timeFrame: Cycle 1 Day 1 predose and up to 24 hours postdose
measure: Area under the plasma concentration versus time curve of TH4000 (prodrug) and TH-4000E (TKI effector)
timeFrame: Cycle 1 Day 1 predose and up to 24 hours postdose
measure: QTc Interval
timeFrame: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination
Other outcomes:
measure: Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging
timeFrame: Baseline
Locations:
city: Los Angeles
country: United States
facility: University of Southern California-Norris
state: California
city: Stanford
country: United States
facility: Stanford school of Medicine
state: California
city: Washington
country: United States
facility: Georgetown Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Bethesda
country: United States
facility: Walter Reed National Military Cancer Center
state: Maryland
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center (VICC)
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: East Melbourne
country: Australia
facility: Peter MacCallum
state: Victoria
Study officials:
affiliation: Georgetown University Hospital Cancer Center
name: Stephen Liu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.