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Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Primary Purpose

Head and Neck Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Clopidogrel
acetylsalicylic acid
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of HPV status.
  2. 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.
  3. Subject's scans have been reviewed at head and neck tumor board to assess tumor involvement.
  4. Subject is 18 years of age or older.
  5. Subject has measurable disease according to RECIST 1.1. Tumor lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions.
  6. Subject has an ECOG performance status of 0 to 2
  7. Subject has estimated life expectancy of at least 3 months.
  8. Subject has adequate hematologic function, defined as:

    1. ANC >1000 K/CUMM
    2. Hemoglobin >8.0 Grams/dL
    3. Platelets >75,000 K/CUMM
    4. INR < 1.7
  9. Subject has adequate renal function, defined as estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula.
  10. Subject has adequate hepatic function, defined as:

    1. Total bilirubin ≤ 1.5 x ULN
    2. AST and ALT ≤ 2.5 x ULN
  11. Female and male subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been post-menopausal for > 1 year.

Note: Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 14 days of registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria:

  1. Subject is receiving concomitant immunosuppressive therapy, defined as:

    1. Immunosuppressants, including: tacrolimus, sirolimus, everolimus, cyclosporine, azathioprine, mycophenolate mofetil, antithymocyte globulin, basiliximab, belatacept
    2. 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.
    3. Chemotherapy
    4. Immunotherapy
    5. Monoclonal antibodies
  2. Concurrent anticancer treatment within 14 days before the start of trial treatment.
  3. Subject has had major surgery within the last 28 days.
  4. Subject has an underlying bleeding disorder.
  5. Subjects requiring re-irradiation to head and neck.
  6. Subject is receiving anticoagulation (see section 7.2 for medication examples). Subjects must have a washout period of 7 days from registration.
  7. Subject has HNSCC with abutment or encasement of the internal carotid artery, external carotid artery or common carotid artery or any of the arterial branches.
  8. Subject has a draining fistula or wound in the head/neck.
  9. Subject with known aneurysm or pseudoaneurysm of the head/neck related to surgery.
  10. Subject has uncontrolled CNS metastases. Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without CNS-directed therapy (such as radiation or surgery) or steroid treatment for for at least 4 weeks prior to registration.
  11. Receipt of any organ transplantation.
  12. Active or history of any autoimmune disease (except type I DM, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment, which are allowed) or immunodeficiencies.
  13. Known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3NCI-CTCAE v4.0), any history of anaphylaxis or uncontrolled asthma.
  14. Subjects who have a hypersensitivity to aspirin or NSAIDs.
  15. Concurrent NSAID therapy (see section 7 for examples). Subjects must have a washout period of 7 days from registration.
  16. Subjects with an acute gastrointestinal ulcer.
  17. Subjects with active hemorrhagic diathesis.
  18. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (NYHA class ≥ II), or serious uncontrolled cardiac arrhythmia.
  19. All other significant diseases, which in the opinion of the investigator, may impair the subject's tolerance of trial treatment.
  20. Vaccination within 4 weeks of the 1st dose of pembrolizumab and while on study is prohibited EXCEPT for administration of inactivated vaccines (e.g. inactivated influenza vaccine).
  21. Women who are pregnant or nursing.

Sites / Locations

  • Medical University of South CarolinaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group 1

Group 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Effect of Pembro + antiplatelet on major cellular parameters
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 Outcome Measures

Effect of Pembro + antiplatelets on immunologic markers
Immunologic markers will be measured in patients who have been treated with two cycles of pembrolizumab alone and who are pembrolizumab naive. Markers will be evaluated by looking at phyenotyping by flow cytometry and changes of 65-panel systemic cytokines and chemokine levels. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes to markers will be reported in aggregate to show the overall immunologic effect of the combination of pembrolizumab + Anti-platelets in patients.
Frequency of adverse events reported
Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0
Tumor response rate
Objective response will be evaluated with computed tomography (CT) of the neck, chest and abdomen at baseline and post-treatment using RECIST 1.1 criteria.

Full Information

First Posted
June 13, 2017
Last Updated
August 10, 2023
Sponsor
Medical University of South Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT03245489
Brief Title
Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Official Title
Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 20, 2017 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
200mg intravenous (IV) over 30 minutes
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
75mg/day oral
Intervention Type
Drug
Intervention Name(s)
acetylsalicylic acid
Other Intervention Name(s)
ASA, aspirin
Intervention Description
81mg/day oral
Primary Outcome Measure Information:
Title
Effect of Pembro + antiplatelet on major cellular parameters
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Effect of Pembro + antiplatelets on immunologic markers
Description
Immunologic markers will be measured in patients who have been treated with two cycles of pembrolizumab alone and who are pembrolizumab naive. Markers will be evaluated by looking at phyenotyping by flow cytometry and changes of 65-panel systemic cytokines and chemokine levels. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes to markers will be reported in aggregate to show the overall immunologic effect of the combination of pembrolizumab + Anti-platelets in patients.
Time Frame
12 weeks
Title
Frequency of adverse events reported
Description
Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0
Time Frame
12 weeks
Title
Tumor response rate
Description
Objective response will be evaluated with computed tomography (CT) of the neck, chest and abdomen at baseline and post-treatment using RECIST 1.1 criteria.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 1.1. 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 Hemoglobin >8.0 Grams/dL Platelets >75,000 K/CUMM INR < 1.7 Subject has adequate renal function, defined as estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula. Subject has adequate hepatic function, defined as: Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Female and male subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been post-menopausal for > 1 year. Note: Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 14 days of registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 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. Subject is receiving anticoagulation (see section 7.2 for medication examples). Subjects must have a washout period of 7 days from registration. Subject has HNSCC with abutment or encasement of the internal carotid artery, external carotid artery or common carotid artery or any of the arterial branches. Subject has a draining fistula or wound in the head/neck. Subject with known aneurysm or pseudoaneurysm of the head/neck related to surgery. Subject has uncontrolled CNS metastases. Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without CNS-directed therapy (such as radiation or surgery) or steroid treatment for for at least 4 weeks prior to registration. Receipt of any organ transplantation. Active or history of any autoimmune disease (except type I DM, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment, which are allowed) or immunodeficiencies. Known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3NCI-CTCAE v4.0), any history of anaphylaxis or uncontrolled asthma. Subjects who have a hypersensitivity to aspirin or NSAIDs. Concurrent NSAID therapy (see section 7 for examples). Subjects must have a washout period of 7 days from registration. Subjects with an acute gastrointestinal ulcer. Subjects with active hemorrhagic diathesis. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (NYHA class ≥ II), or serious uncontrolled cardiac arrhythmia. All other significant diseases, which in the opinion of the investigator, may impair the subject's tolerance of trial treatment. Vaccination within 4 weeks of the 1st dose of pembrolizumab and while on study is prohibited EXCEPT for administration of inactivated vaccines (e.g. inactivated influenza vaccine). Women who are pregnant or nursing.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina Godwin
Phone
843-792-8876
Email
hcc-clinical-trials@musc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Kaczmar, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Godwin
Phone
843-792-8876
Email
hcc-clinical-trials@musc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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