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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01334177
First received: March 21, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: TLR8 agonist VTX-2337
Biological: cetuximab
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Maximum tolerated dose and the toxicities of TLR8 agonist VTX-2337 in combination with cetuximab [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacodynamic immune response to TLR8 agonist VTX-2337 in combination with cetuximab [ Time Frame: Day 1 of Course 1 ] [ Designated as safety issue: No ]
    Will be predominantly descriptive with graphical information where available.


Estimated Enrollment: 13
Study Start Date: June 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (immunotherapy and monoclonal antibody therapy)
Patients 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.
Drug: TLR8 agonist VTX-2337
Given SC
Other Names:
  • Toll-like receptor 8 agonist VTX-2337
  • VTX-2337
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

    • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334177

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Laura Q. Chow    206-288-6968      
Principal Investigator: Laura Q. Chow         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Laura Chow Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01334177     History of Changes
Other Study ID Numbers: 7406, NCI-2011-00240, 7406, P30CA015704
Study First Received: March 21, 2011
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Laryngeal Diseases
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Tongue Neoplasms
Carcinoma, Verrucous
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Salivary Gland Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms

ClinicalTrials.gov processed this record on July 26, 2014