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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1NCT01334177

TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck

A Phase 1 study testing TLR8 agonist VTX-2337, cetuximab and laboratory biomarker analysis in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Metastatic Squamous Neck Cancer With Occult Primary, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TLR8 agonist VTX-2337, cetuximab and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Jun 2011to Jun 2014
Phase
Phase 1
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

  • 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
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  • 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
  • For patients with liver metastases, AST, ALT < 5x ULN is acceptable
  • Willingness to use a medically acceptable method of contraception throughout the study period and for 4 weeks after the final administration of VTX-2337 (all subjects)
  • For female subjects with reproductive potential: a negative serum pregnancy test

Who cannot join

  • 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
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  • 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
  • Known prior severe allergic/hypersensitivity to cetuximab or any of the components of the study treatment
  • Known prior severe (>= Grade 3) rash and / or diarrhea toxicities to cetuximab

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety, tolerability and to assess the dose-limiting toxicities (DLT) of VTX-2337 (TLR8 Agonist VTX-2337) when given in conjunction with cetuximab in order to define the maximum tolerated dose (MTD)/recommended phase II dose (RP2D).

SECONDARY OBJECTIVES:

  1. To determine the pharmacodynamic immune response to VTX-2337 in combination with cetuximab.

II. Correlative assessments of immunologic response and activity will be performed, including: Quantitative evaluation of baseline immune status via in-vitro assessment of cytokine and chemokine response to immunostimulatory agents; quantitative assessment of plasma cytokines, chemokines, and other inflammatory markers via protein array; quantitative assessment of natural killer (NK) cells via flow cytometry; quantitative assessment of antigen-specific responses in cytokine-producing cells to common prognostic SCCHN antigens via interferon (INF)gamma-enzyme-linked immunosorbent spot (ELISpot).

III. To assess whether subjects with functional genetic variations in the TLR8 and FC-gamma-R IIIA genes have altered biological and/or clinical responses to VTX-2337, genetic characterization of subjects will be performed via standard genotyping assays.

TERTIARY OBJECTIVES:

  1. To assess preliminary evidence of anti-tumor activity for the combination of VTX-2337 and cetuximab, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

OUTLINE: This is a dose-escalation study of TLR8 Agonist VTX-2337.

Patients receive cetuximab intravenously (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 subcutaneously (SC) on days 1, 8, 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

Being tested
TLR8 agonist VTX-2337, cetuximab, laboratory biomarker analysis, pharmacogenomic studies
Medical subject headings
Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TLR8 agonist VTX-2337Drug

    Also called Toll-like receptor 8 agonist VTX-2337, VTX-2337

    Given SC

  • cetuximabBiological

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacogenomic studiesOther

    Also called Pharmacogenomic Study

    Correlative studies

Study groups in NCT01334177
Study groupRoleWhat they receive
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.
Receives: Drug: TLR8 agonist VTX-2337; Biological: cetuximab; Other: laboratory biomarker analysis; Other: pharmacogenomic studies

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 28 days

Secondary outcomes (1)

  1. Pharmacodynamic immune response to TLR8 agonist VTX-2337 in combination with cetuximab

    Will be predominantly descriptive with graphical information where available.

    Measured: Day 1 of Course 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionJun 2014

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01334177
Sponsor's protocol ID
7406
Other IDs
NCI-2011-00240, 7406, P30CA015704
Status last verified
Mar 2015
First submitted
21 Mar 2011
Last updated
5 Mar 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 26928328

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TLR8 agonist VTX-2337, cetuximab and laboratory biomarker analysis in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Metastatic Squamous Neck Cancer With Occult Primary, run by University of Washington at 1 site in United States.

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 18 inclusion and 17 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: finished, as of the sponsor's last update on 5 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose and the toxicities of TLR8 agonist VTX-2337 in combination with cetuximab (time frame: 28 days). 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 NCT01334177, 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 5 Mar 2015.

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