Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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

Study Overview

• Status: Completed
• Conditions: Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and Neck Carcinoma; Cancer of Head and Neck; Head and Neck Cancer Metastatic; Head and Neck Cancer Stage IV; Cancer of Esophagus; Cancer, Metastatic; Head and Neck Cancer Stage III; Cancer of Mouth; Cancer of Neck
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Tadalafil

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Keytruda; Drug: Tadalafil; 10 mg by mouth daily; Other Names: Cialis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Dose Limiting Toxicity (DLT)	Rate of dose limiting toxicity at least possibly attributable to study treatment	2 years
Overall Survival (OS)	Overall survival at 12 months post-enrollment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Measured by RECIST 1.1	Response measured by RECIST 1.1	12 months
Progression Free Survival	Progression free survival	2 years
Adverse Event Rates	Adverse event rates	2 years

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Joseph Califano, UCSD

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2020
• Primary Completion (Actual): April 16, 2022
• Study Completion (Actual): January 9, 2024

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 20, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: carcinoma; immunotherapy; cancer; metastatic; pembrolizumab; tadalafil; opdivo; cialis; pd-1; pde
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Esophageal Diseases; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Carcinoma; Esophageal Neoplasms; Neoplasm Metastasis; Head and Neck Neoplasms; Mouth Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Pyridoxine-dependent epilepsy; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil; pembrolizumab
• Other Study ID Numbers: 190098

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.: Yes