Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Head and Neck Cancer
- Sponsor
- Medical University of South Carolina
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Effect of Pembro + antiplatelet on major cellular parameters
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to see if anti-platelet therapy combined with anti-PD-1 immunotherapy can cause a more favorable immunologic response thatn with immunotherapy alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of HPV status.
- •Subject has tumor that expresses PD-L1 (Combined Positive Score \[CPS\] \> 1) as determined by an FDA-approved test or subject has experienced disease progression on or after platinum-containing chemotherapy.
- •Subject's scans have been reviewed at head and neck tumor board to assess tumor involvement.
- •Subject is 18 years of age or older.
- •Subject has measurable disease according to RECIST 1.
- •Tumor lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions.
- •Subject has an ECOG performance status of 0 to 2
- •Subject has estimated life expectancy of at least 3 months.
- •Subject has adequate hematologic function, defined as:
- •ANC \>1000 K/CUMM
Exclusion Criteria
- •Subject is receiving concomitant immunosuppressive therapy, defined as:
- •Immunosuppressants, including: tacrolimus, sirolimus, everolimus, cyclosporine, azathioprine, mycophenolate mofetil, antithymocyte globulin, basiliximab, belatacept
- •Systemic corticosteroids (except for short term treatment of allergic reactions or for treatment of irAE). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
- •Chemotherapy
- •Immunotherapy
- •Monoclonal antibodies
- •Concurrent anticancer treatment within 14 days before the start of trial treatment.
- •Subject has had major surgery within the last 28 days.
- •Subject has an underlying bleeding disorder.
- •Subjects requiring re-irradiation to head and neck.
Arms & Interventions
Group 1
Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.
Intervention: Pembrolizumab
Group 1
Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.
Intervention: Clopidogrel
Group 1
Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.
Intervention: acetylsalicylic acid
Group 2
Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.
Intervention: Pembrolizumab
Group 2
Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.
Intervention: Clopidogrel
Group 2
Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.
Intervention: acetylsalicylic acid
Outcomes
Primary Outcomes
Effect of Pembro + antiplatelet on major cellular parameters
Time Frame: 12 weeks
Immunologic response profile will be measured by changes in major cellular parameters in peripheral blood mononuclear cells pheotyped by flow cytometry for MDSCs, T and B cell activation markers and polyclonal IFNy-production by CD4 and CD8 response after P/I stimulation) in pembrolizumab alone and pembrolizumab + antiplatelet therapy. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes in cellular parameters from the previous timepoint will be evaluated using a repeated measures ANOVA model. Cellular parameters will be evaluated in aggregate to report the immunologic response.
Secondary Outcomes
- Frequency of adverse events reported(12 weeks)
- Tumor response rate(12 weeks)
- Effect of Pembro + antiplatelets on immunologic markers(12 weeks)