Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin
Primary Purpose
Metastatic Head-and-neck Squamous-cell Carcinoma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TH-4000 (Tarloxotinib)
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Head-and-neck Squamous-cell Carcinoma focused on measuring squamous cell carcinoma, the head and neck, skin, TH-4000, Hypoxia, Tarloxotinib
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
Sites / Locations
- University of Southern California-Norris
- Stanford school of Medicine
- Georgetown Medical Center
- University of Chicago
- Walter Reed National Military Cancer Center
- Fox Chase Cancer Center
- Vanderbilt-Ingram Cancer Center (VICC)
- UT Southwestern Medical Center
- Chris O'Brien Lifehouse
- Peter MacCallum
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TH-4000 (Tarloxotinib)
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of participants with response rate as evaluated by RECIST criteria
Secondary Outcome Measures
Incidence of adverse events (AEs)
Type of adverse events (AEs)
Severity of adverse events (AEs)
Duration of response (DOR) calculated for all patients achieving an objective response
Progression-free survival (PFS)
Overall Survival (OS)
Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector)
Area under the plasma concentration versus time curve of TH4000 (prodrug) and TH-4000E (TKI effector)
QTc Interval
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02449681
Brief Title
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
August 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rain Oncology Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Head-and-neck Squamous-cell Carcinoma
Keywords
squamous cell carcinoma, the head and neck, skin, TH-4000, Hypoxia, Tarloxotinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label single arm two-stage, phase-2 study
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TH-4000 (Tarloxotinib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TH-4000 (Tarloxotinib)
Other Intervention Name(s)
Tarloxotinib
Primary Outcome Measure Information:
Title
Number of participants with response rate as evaluated by RECIST criteria
Time Frame
Approximately 12 months
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Type of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Severity of adverse events (AEs)
Time Frame
Up to 30 days after last dose
Title
Duration of response (DOR) calculated for all patients achieving an objective response
Time Frame
Approximately 12 months
Title
Progression-free survival (PFS)
Time Frame
Approximately 12 months
Title
Overall Survival (OS)
Time Frame
Approximately 12 months
Title
Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector)
Time Frame
Cycle 1 Day 1 predose and up to 24 hours postdose
Title
Area under the plasma concentration versus time curve of TH4000 (prodrug) and TH-4000E (TKI effector)
Time Frame
Cycle 1 Day 1 predose and up to 24 hours postdose
Title
QTc Interval
Time Frame
Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination
Other Pre-specified Outcome Measures:
Title
Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Liu
Organizational Affiliation
Georgetown University Hospital Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California-Norris
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford school of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Georgetown Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Walter Reed National Military Cancer Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center (VICC)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Peter MacCallum
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
35435625
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.
Results Reference
derived
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Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin
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