TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck
Phase I Clinical Trial of VTX-2337, a Small Molecule Toll-Like Receptor 8 (TLR8) Agonist in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinomas of the Head and Neck (SCCHN)
3 other identifiers
interventional
13
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of TLR8 Agonist VTX-2337 when given together with cetuximab in treating patients with locally advanced, recurrent, or metastatic squamous cell cancer of the head and neck (SCCHN). Biological therapies, such as TLR8 Agonist VTX-2337 may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving TLR8 Agonist VTX-2337 together with cetuximab may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 21, 2011
CompletedFirst Posted
Study publicly available on registry
April 13, 2011
CompletedStudy Start
First participant enrolled
June 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedMarch 5, 2015
March 1, 2015
3 years
March 21, 2011
March 3, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose and the toxicities of TLR8 agonist VTX-2337 in combination with cetuximab
Frequency and severity of hematologic and non-hematologic adverse events will be compiled for each dose cohort. Assessment of adverse events will include type, incidence, severity (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0), duration, seriousness, and relatedness; and clinically significant laboratory abnormalities.
28 days
Secondary Outcomes (1)
Pharmacodynamic immune response to TLR8 agonist VTX-2337 in combination with cetuximab
Day 1 of Course 1
Study Arms (1)
Treatment (immunotherapy and monoclonal antibody therapy)
EXPERIMENTALPatients receive cetuximab IV over 60-120 minutes on days -28, -21, -14, -7 of weeks -4 to -1. Patients then receive cetuximab IV on days 1, 8, 15, and 22 and TLR8 agonist VTX-2337 SC on days 1, 8, 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given SC
Given IV
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients with a histological or cytopathological confirmed diagnosis of squamous cell carcinoma of the head and neck region that is:
- Locally advanced/recurrent and no longer amenable to local surgical or radiation therapy and/or
- Has evidence of metastatic disease
- Patients may have been previously treated with systemic therapy but are otherwise deemed currently platinum-refractory, or would be deemed inappropriate or intolerant to platinum-based chemotherapy
- Patients must have completed definitive chemotherapy and/or radiation therapy \>= 3 months prior to study entry
- Prior therapy with agents targeting/blocking the epidermal growth factor receptor (e.g. cetuximab and erlotinib) is allowable
- Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 - 2
- Expected life expectancy of at least 12 weeks, as assessed by the Investigator
- Ability and willingness to comply with the study's visit and assessment schedule and to provide voluntary written informed consent
- Absolute neutrophil count (ANC) \>= 1,500 cells/μL
- Platelet count \>= 75,000 cells/μL
- Hemoglobin \>= 8.0 g/dL
- Creatinine =\< 2.0 mg/dL
- Total bilirubin =\< 2.0 x upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]), serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN
- +3 more criteria
You may not qualify if:
- Investigational therapy within 4 weeks of study entry
- Chemotherapy therapy or palliative radiation therapy within the previous 2 weeks prior to dosing with cetuximab or VTX-2337; patients should have recovered from major toxicities of prior therapy (If deemed reversible, toxicities should return to baseline or =\< grade 2 in severity)
- Major surgery within the past 4 weeks prior to dosing with cetuximab or VTX-2337
- Concurrent symptomatic central nervous system (CNS) involvement, brain or leptomeningeal metastases; treated CNS involvement which has been stable \> 28 days off systemic steroids may be included
- Major active psychiatric disorders which would limit compliance
- Treatment with oral or parenteral corticosteroids within 2 weeks prior to dosing with VTX-2337 or a requirement for systemic immunosuppressive therapy for any reason
- Active autoimmune disease
- Clinically significant cardiac disease (e.g., congestive heart failure, unstable or uncontrolled angina, myocardial infarction) within 6 months of dosing with VTX-2337
- Clinically significant ophthalmologic disease, defined as:
- Current retinal vascular disorder, including active untreated diabetic retinopathy and/or
- Previous or current uveitis
- Infection requiring parenteral antibiotic therapy or causing fever (temp \> 100.5 degrees Fahrenheit \[F\] or 38.1 degrees Celsius \[C\]) within 1 week prior to dosing with VTX-2337
- Pregnant or breast-feeding females
- Uncontrolled inter-current illness, pre-planned surgery or procedure requiring hospitalization during the study period, or any other condition or circumstance that could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives
- Second primary malignancy that is clinically detectable (not including in situ carcinoma of the cervix, non-melanoma skin cancer or low-grade \[Gleason score =\< 6\] localized prostate cancer) and demonstrating active progression at the time of consideration for study enrollment
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (1)
Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, Hershberg RM. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity. PLoS One. 2016 Feb 29;11(2):e0148764. doi: 10.1371/journal.pone.0148764. eCollection 2016.
PMID: 26928328DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Chow
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 21, 2011
First Posted
April 13, 2011
Study Start
June 1, 2011
Primary Completion
June 1, 2014
Last Updated
March 5, 2015
Record last verified: 2015-03