Back to resultsA Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Motolimod
Cetuximab
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck
Eligibility Criteria
Inclusion Criteria:
- Previously untreated stage II, III, or IVA histologically or cytologically confirmed squamous cell carcinoma of the head and neck
- Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx
- Macroscopic complete resection of the primary tumor must be planned
- Age ≥ 18 years
- ECOG performance status 0-1
- Adequate hematologic, renal and hepatic function
- Have signed written informed consent
Exclusion Criteria:
- Subjects who fail to meet inclusion criteria
- Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
- Prior severe infusion reaction to a monoclonal antibody
- Pregnancy or breastfeeding
- Evidence of distant metastasis
- Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast
- Prior history of head and neck cancer
- Prior therapy with motolimod, nivolumab, or other agents targeting PD-1/PD-L1
- Prior therapy targeting the EGFR pathway
- Acute hepatitis, known HIV, or active uncontrolled infection
- Patients with active autoimmune disease
- History of uncontrolled cardiac disease within prior 6 months
- Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months
- Active alcohol abuse or other illness or circumstance that carries a likelihood of inability to comply with study treatment and follow-up or otherwise compromise the study's objectives
- Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment
- Live vaccine within 30 days of planned start of study therapy
- History of pneumonitis or interstitial lung disease
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
Sites / Locations
- University of Pittsburgh Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Motolimod plus cetuximab
Motolimod, cetuximab, and nivolumab
Arm Description
Cohort 1: motolimod plus cetuximab
Cohort 2: motolimod, cetuximab, and nivolumab
Outcomes
Primary Outcome Measures
The change in immune biomarkers including FcγR genotype, NK activation, tumor infiltration and serum cytokines, mDC, T cell activation, and tumor-antigen specific cytotoxic T lymphocyte induction.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02124850
Brief Title
A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab
Official Title
A Phase Ib Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Plus Motolimod and With Cetuximab Plus Motolimod Plus Nivolumab
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Study Start Date
October 28, 2014 (Actual)
Primary Completion Date
August 11, 2016 (Actual)
Study Completion Date
October 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Protocol VRXP-A106 will enroll patients with Stage II-IVA head and neck cancer patients who will be treated with surgical resection. Cetuximab and motolimod (Cohort 1); and cetuximab, motolimod, and nivolumab (Cohort 2) will be administered for a 3-4 week period before surgery. The primary objective of the study is to determine the extent to which the administration of neoadjuvant motolimod plus cetuximab and motolimod plus cetuximab and nivolumab modulates immune biomarkers (NK, mDC and T cell activation as well as tumor infiltration and serum cytokines) in peripheral blood and head and neck cancer tumors. An exploratory objective of the study is to assess whether modulation of biomarkers as described above can predict anti-tumor response.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Motolimod plus cetuximab
Arm Type
Experimental
Arm Description
Cohort 1: motolimod plus cetuximab
Arm Title
Motolimod, cetuximab, and nivolumab
Arm Type
Experimental
Arm Description
Cohort 2: motolimod, cetuximab, and nivolumab
Intervention Type
Drug
Intervention Name(s)
Motolimod
Other Intervention Name(s)
VTX-2337
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Primary Outcome Measure Information:
Title
The change in immune biomarkers including FcγR genotype, NK activation, tumor infiltration and serum cytokines, mDC, T cell activation, and tumor-antigen specific cytotoxic T lymphocyte induction.
Time Frame
change from baseline to up to 4 weeks
Other Pre-specified Outcome Measures:
Title
Anti-tumor response
Time Frame
Change from baseline to pre-surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previously untreated stage II, III, or IVA histologically or cytologically confirmed squamous cell carcinoma of the head and neck
Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx
Macroscopic complete resection of the primary tumor must be planned
Age ≥ 18 years
ECOG performance status 0-1
Adequate hematologic, renal and hepatic function
Have signed written informed consent
Exclusion Criteria:
Subjects who fail to meet inclusion criteria
Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
Prior severe infusion reaction to a monoclonal antibody
Pregnancy or breastfeeding
Evidence of distant metastasis
Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast
Prior history of head and neck cancer
Prior therapy with motolimod, nivolumab, or other agents targeting PD-1/PD-L1
Prior therapy targeting the EGFR pathway
Acute hepatitis, known HIV, or active uncontrolled infection
Patients with active autoimmune disease
History of uncontrolled cardiac disease within prior 6 months
Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months
Active alcohol abuse or other illness or circumstance that carries a likelihood of inability to comply with study treatment and follow-up or otherwise compromise the study's objectives
Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment
Live vaccine within 30 days of planned start of study therapy
History of pneumonitis or interstitial lung disease
History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amar Patel, MD
Organizational Affiliation
Celgene
Official's Role
Study Director
Facility Information:
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
12. IPD Sharing Statement
Citations:
Citation
https://clincancerres.aacrjournals.org/content/clincanres/early/2017/11/28/1078-0432.CCR-17-0357.full.pdf
Results Reference
result
Learn more about this trial
A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab
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