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Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03993353
Recruitment Status : Recruiting
First Posted : June 20, 2019
Last Update Posted : June 23, 2021
Information provided by (Responsible Party):
Joseph Califano, University of California, San Diego

Brief Summary:
This study will examine the combination of pembrolizumab and tadalafil for safety and efficacy in advanced head and neck cancer.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Head and Neck Carcinoma Head and Neck Cancer Stage III Head and Neck Cancer Stage IV Head and Neck Cancer Metastatic Cancer Cancer of Esophagus Cancer, Metastatic Cancer of Head and Neck Cancer of Mouth Cancer of Neck Drug: Pembrolizumab Drug: Tadalafil Phase 2

Detailed Description:

Immune competent animal models of HNSCC demonstrate that combination PDE-5 inhibitor (tadalafil) and PD-1 inhibitor therapy is more effective than either therapy alone based on the concept of targeting multiple immune repressive abnormalities simultaneously (PD-1 checkpoint and myeloid suppressive pathways).

This trial will test the hypothesis that combination PD-1 inhibition and PDE-5 inhibition can be safely co-administered, and secondarily test the hypothesis that the combination of both therapies will be more effective than PD-1 inhibition alone in recurrent/metastatic HNSCC.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : April 7, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Tadalafil and Pembrolizumab
Tadalafil for up to 12 months and pembrolizumab for up to 24 months.
Drug: Pembrolizumab
200 mg intravenously every 3 weeks
Other Name: Keytruda

Drug: Tadalafil
10 mg by mouth daily
Other Name: Cialis

Primary Outcome Measures :
  1. Rate of Dose Limiting Toxicity (DLT) [ Time Frame: 2 years ]
    Rate of dose limiting toxicity at least possibly attributable to study treatment

  2. Overall Survival (OS) [ Time Frame: 12 months ]
    Overall survival at 12 months post-enrollment

Secondary Outcome Measures :
  1. Response measured by RECIST 1.1 [ Time Frame: 12 months ]
  2. Progression free survival [ Time Frame: 2 years ]
  3. Adverse event rates [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Selected Inclusion Criteria:

  • Patients (at least 18 years of age) must have recurrent or metastatic squamous cell carcinoma of the head and neck.
  • Presence of measurable disease.
  • Life expectancy of greater than 12 weeks
  • Patients must have normal organ and marrow function

Selected Exclusion Criteria:

  • Prior therapy with an PD-1 or PD-L1 inhibitor in the recurrent or metastatic setting
  • Uncontrolled central nervous system metastases (stable metastases permitted)
  • Active autoimmune disease
  • Chemotherapy ≤28 days prior to first administration of study treatment and/or monoclonal antibody ≤8 weeks prior to first administration of study treatment.
  • Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater within 3 months of trial enrollment
  • Current use of all other long-acting PDE5 inhibitors.
  • Known severe hypersensitivity to tadalafil or any of the excipients of this product
  • Current treatment with nitrates
  • Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir.
  • Current treatment with guanylate cyclase (GC) stimulators such as riociguat.
  • History of hypotension and/or blindness and/or sensorineural hearing loss during prior treatment with tadalafil or other PDE-5 inhibitors
  • History of known hereditary degenerative retinal disorders, including retinitis pigmentosa
  • Prior history of non-arteritic anterior ischemic optic neuropathy
  • Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.
  • History of stroke within prior 6 months.
  • History of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure
  • Left ventricular outflow obstructions, such as aortic stenosis and idiopathic hypertrophic subaortic stenosis
  • Angina requiring treatment with long-acting nitrates
  • Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration
  • Unstable angina within 90 days of visit 1 (Braunwald 1989)
  • Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention
  • History of any of the following coronary conditions within 90 days of planned tadalafil administration:

    • Myocardial Infarction
    • Coronary artery bypass graft surgery
    • Percutaneous coronary intervention (for example, angioplasty or stent placement)
    • Any evidence of heart disease (NYHA ≥ Class II as defined in Protocol Attachment LVHG.3) within 6 months of planned tadalafil administration
  • Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent)
  • Prior organ transplantation
  • Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).

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 identifier (NCT number): NCT03993353

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Contact: Khushbu Singh (858) 246-2604

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United States, California
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: CTO   
Sponsors and Collaborators
University of California, San Diego
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Principal Investigator: Joseph Califano UCSD
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Responsible Party: Joseph Califano, Professor of Medicine, University of California, San Diego Identifier: NCT03993353    
Other Study ID Numbers: 190098
First Posted: June 20, 2019    Key Record Dates
Last Update Posted: June 23, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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.: Yes
Keywords provided by Joseph Califano, University of California, San Diego:
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Esophageal Neoplasms
Mouth Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Mouth Diseases
Stomatognathic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents