Metastatic Head-and-neck Squamous-cell CarcinomaPhase 2NCT02449681
Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin
A Phase 2 study testing TH-4000 (Tarloxotinib) in people with Metastatic Head-and-neck Squamous-cell Carcinoma, run by Rain Oncology Inc at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Head-and-neck Squamous-cell Carcinoma
- What is being tested?
- TH-4000 (Tarloxotinib)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Aug 2015to 31 Jan 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States8 sites
Walter Reed National Military Cancer Center
Bethesda, Maryland, 20889
University of Chicago
Chicago, Illinois, 60637
UT Southwestern Medical Center
Dallas, Texas, 75390
University of Southern California-Norris
Los Angeles, California, 90033
Vanderbilt-Ingram Cancer Center (VICC)
Nashville, Tennessee, 37232
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19104
Stanford school of Medicine
Stanford, California, 94305
Georgetown Medical Center
Washington D.C., District of Columbia, 20007
Australia2 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Peter MacCallum
East Melbourne, Victoria, 3002
About this study
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
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.
Read the 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.
- Being tested
- TH-4000 (Tarloxotinib)
- Keywords
- squamous cell carcinoma, the head and neck, skin, TH-4000, Hypoxia, Tarloxotinib
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-4000 (Tarloxotinib)Drug
Also called Tarloxotinib
| Study group | Role | What they receive |
|---|---|---|
| TH-4000 (Tarloxotinib) | Experimental | 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. Receives: Drug: TH-4000 (Tarloxotinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with response rate as evaluated by RECIST criteria
Measured: Approximately 12 months
Secondary outcomes (9)
Incidence of adverse events (AEs)
Measured: Up to 30 days after last dose
Type of adverse events (AEs)
Measured: Up to 30 days after last dose
Severity of adverse events (AEs)
Measured: Up to 30 days after last dose
Duration of response (DOR) calculated for all patients achieving an objective response
Measured: Approximately 12 months
Progression-free survival (PFS)
Measured: Approximately 12 months
Overall Survival (OS)
Measured: Approximately 12 months
Maximum plasma concentration of TH-4000 (prodrug) and TH-4000E (TKI effector)
Measured: 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)
Measured: Cycle 1 Day 1 predose and up to 24 hours postdose
QTc Interval
Measured: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2015 (estimated)
- Study startAug 2015
- Primary completionJan 2017
- Study completion31 Jan 2017
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Head-and-neck Squamous-cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label single arm two-stage, phase-2 study
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rain Oncology Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Liu, Principal investigator, Georgetown University Hospital Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02449681
- Sponsor's protocol ID
- TH-CR-602
- Status last verified
- Jan 2023
- First submitted
- 12 May 2015
- Last updated
- 12 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 35435625
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02449681
- Acronym / sponsor ID
- TH-CR-602
- Keywords
- squamous cell carcinoma, the head and neck, skin, TH-4000, Hypoxia, Tarloxotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Rain Oncology IncIndustry (pharma, biotech, devices)
- Study start
- Aug 2015
- Primary completion
- Jan 2017 (actual)
- Study completion
- 31 Jan 2017 (actual)
- First posted
- 20 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label single arm two-stage, phase-2 study
| Arm | Type | Receives |
|---|---|---|
| TH-4000 (Tarloxotinib) | Experimental | Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TH-4000 (Tarloxotinib)Also: Tarloxotinib | Drug | TH-4000 (Tarloxotinib) |
Primary outcome
Number of participants with response rate as evaluated by RECIST criteria
Time frame: Approximately 12 months
9 secondary outcomes
Incidence of adverse events (AEs)
Time frame: Up to 30 days after last dose
Type of adverse events (AEs)
Time frame: Up to 30 days after last dose
Severity of adverse events (AEs)
Time frame: Up to 30 days after last dose
Duration of response (DOR) calculated for all patients achieving an objective response
Time frame: Approximately 12 months
Progression-free survival (PFS)
Time frame: Approximately 12 months
Overall Survival (OS)
Time frame: Approximately 12 months
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
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
QTc Interval
Time frame: Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 and study Termination
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
- Derived from this study: PubMed 35435625McLean 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Liu principal investigator
Georgetown University Hospital Cancer Center
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TH-4000 (Tarloxotinib) in people with Metastatic Head-and-neck Squamous-cell Carcinoma, run by Rain Oncology Inc at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with response rate as evaluated by RECIST criteria (time frame: Approximately 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02449681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2023.