Anti-platelet + Pembro for H&N Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Clopidogrel; Drug: acetylsalicylic acid

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Pembrolizumab; 200mg intravenous (IV) over 30 minutes; Other Names: Keytruda; Drug: Clopidogrel; 75mg/day oral; Other Names: Plavix; Drug: acetylsalicylic acid; 81mg/day oral; Other Names: ASA; aspirin
Experimental: 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.	Drug: Pembrolizumab; 200mg intravenous (IV) over 30 minutes; Other Names: Keytruda; Drug: Clopidogrel; 75mg/day oral; Other Names: Plavix; Drug: acetylsalicylic acid; 81mg/day oral; Other Names: ASA; aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks
Frequency of adverse events reported	Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0	12 weeks
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.	12 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: John Kaczmar, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: August 9, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin; Pembrolizumab
• Other Study ID Numbers: 102727

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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