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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

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ClinicalTrials.gov Identifier: NCT03245489
Recruitment Status : Recruiting
First Posted : August 10, 2017
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Medical University of South Carolina

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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Drug: Pembrolizumab Drug: Clopidogrel Drug: acetylsalicylic acid Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Actual Study Start Date : October 20, 2017
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2020

Resource links provided by the National Library of Medicine


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 Name: Keytruda

Drug: Clopidogrel
75mg/day oral
Other Name: 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 Name: Keytruda

Drug: Clopidogrel
75mg/day oral
Other Name: Plavix

Drug: acetylsalicylic acid
81mg/day oral
Other Names:
  • ASA
  • aspirin




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Effect of Pembro + antiplatelets on immunologic markers [ Time Frame: 12 weeks ]
    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.

  2. Frequency of adverse events reported [ Time Frame: 12 weeks ]
    Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0

  3. Tumor response rate [ Time Frame: 12 weeks ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of HPV status or PDL-1 status.
  2. 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 3 days prior to receiving therapy. 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 team 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 28 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). Washout period of 7 days.
  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.
  10. Active or history of CNS metastases.
  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). Washout period of 7 days.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03245489


Contacts
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Contact: Brittanie Weinerman 843-792-9321 hcc-clinical-trials@musc.edu

Locations
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United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Brittanie Weinerman    843-792-9321    hcc-clinical-trials@musc.edu   
Sponsors and Collaborators
Medical University of South Carolina
Investigators
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Principal Investigator: Carolyn Britten, MD Medical University of South Carolina

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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT03245489     History of Changes
Other Study ID Numbers: 102727
First Posted: August 10, 2017    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Additional relevant MeSH terms:
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Platelet Aggregation Inhibitors
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Pembrolizumab
Clopidogrel
Aspirin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents