Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer
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ClinicalTrials.gov Identifier: NCT03993353 |
Recruitment Status :
Recruiting
First Posted : June 20, 2019
Last Update Posted : June 23, 2021
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Condition or disease | Intervention/treatment | Phase |
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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 |
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.
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.
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Drug: Pembrolizumab
200 mg intravenously every 3 weeks
Other Name: Keytruda Drug: Tadalafil 10 mg by mouth daily
Other Name: Cialis |
- Rate of Dose Limiting Toxicity (DLT) [ Time Frame: 2 years ]Rate of dose limiting toxicity at least possibly attributable to study treatment
- Overall Survival (OS) [ Time Frame: 12 months ]Overall survival at 12 months post-enrollment
- Response measured by RECIST 1.1 [ Time Frame: 12 months ]
- Progression free survival [ Time Frame: 2 years ]
- Adverse event rates [ Time Frame: 2 years ]

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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
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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).

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): NCT03993353
Contact: Khushbu Singh | (858) 246-2604 | ksingh@health.ucsd.edu |
United States, California | |
UCSD Moores Cancer Center | Recruiting |
La Jolla, California, United States, 92093 | |
Contact: CTO CancerCTO@ucsd.edu |
Principal Investigator: | Joseph Califano | UCSD |
Responsible Party: | Joseph Califano, Professor of Medicine, University of California, San Diego |
ClinicalTrials.gov 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 |
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 |
cancer pembrolizumab tadalafil cialis opdivo |
immunotherapy metastatic carcinoma pd-1 pde |
Carcinoma 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 Neoplasms, Squamous Cell Neoplasms by Site Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases |
Esophageal Diseases Gastrointestinal Diseases Mouth Diseases Stomatognathic Diseases Pembrolizumab Tadalafil Antineoplastic Agents, Immunological Antineoplastic Agents Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Urological Agents |