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Pembrolizumab, Aspirin, and Clopidogrel Bisulfate in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Trial Status: Active

This randomized phase I trial studies how well pembrolizumab, aspirin, and clopidogrel bisulfate work in treating patients with head and neck squamous cell carcinoma that has come back or that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Aspirin and clopidogrel bisulfate are a type of drug called anti-platelets that help prevent blood clots. Giving pembrolizumab, aspirin, and clopidogrel bisulfate together may work better in treating patients with head and neck squamous cell carcinoma.

Inclusion Criteria

  • Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of human papillomavirus (HPV) status or PDL-1 status
  • Subject has experienced disease progression on or after platinum-containing chemotherapy
  • Subject has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; tumor lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Subject has estimated life expectancy of at least 3 months
  • ANC >= 1000 K/CUMM
  • Hemoglobin >= 8.0 grams/dL
  • Platelets >= 75,000 K/CUMM
  • International normalized ratio (INR) =< 1.7
  • Estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (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 prior to 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 team treatment of allergic reactions or for treatment of immune related adverse events [irAE]); steroids with no or minimal systemic effect (topical, inhalation) are allowed * Chemotherapy * Immunotherapy * Monoclonal antibodies
  • Concurrent anticancer treatment within 28 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; 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.
  • Active or history of central nervous system (CNS) metastases
  • Receipt of any organ transplantation
  • Active or history of any autoimmune disease (except type I diabetes mellitus [DM], vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment, which are allowed) or immunodeficiencies
  • Known severe hypersensitivity reactions to monoclonal antibodies (grade >= 3 National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version [v]4.0), any history of anaphylaxis or uncontrolled asthma
  • Subjects who have a hypersensitivity to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
  • Concurrent NSAID therapy; subjects must have 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 (New York Heart Association [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

South Carolina

Medical University of South Carolina
Status: ACTIVE
Contact: John M. Kaczmar
Phone: 843-792-4271


I. To determine if anti-platelet therapy (aspirin [acetylsalicylic acid], clopidogrel bisulfate [clopidogrel]) combined with anti-PD-1 immunotherapy (pembrolizumab) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) is able to induce a more favorable immunologic response profile than immunotherapy alone.


I. To evaluate changes in immune response profiles with pembrolizumab alone and with pembrolizumab + anti-platelet therapy.

II. To evaluate the effect of pembrolizumab + anti-platelet therapy in patients already treated with two cycles of single agent pembrolizumab and those who are pembrolizumab naive.

III. To determine potential toxicities of combined anti-platelet and immunotherapy in patients with HNSCC.

IV. To determine the response rate of anti-platelet therapy in combination with immunotherapy in patients with recurrent or metastatic HNSCC.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP 1: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, aspirin orally (PO) daily on days 1-21, and clopidogrel bisulfate PO daily on days 1-21. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then cross-over to Group 2.

GROUP 2: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then cross-over to Group 1.

After completion of study treatment, patients are followed up for 12 weeks.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Medical University of South Carolina

Principal Investigator
John M. Kaczmar

  • Primary ID 102727
  • Secondary IDs NCI-2017-02450
  • ID NCT03245489