Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

March 11, 2024 updated by: Joseph Califano, University of California, San Diego

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

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 (Estimated)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
200 mg intravenously every 3 weeks
Other Names:
  • Keytruda
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)
Time Frame: 2 years
Rate of dose limiting toxicity at least possibly attributable to study treatment
2 years
Overall Survival (OS)
Time Frame: 12 months
Overall survival at 12 months post-enrollment
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression free survival
Time Frame: 2 years
2 years
Response measured by RECIST 1.1
Time Frame: 12 months
12 months
Adverse event rates
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Joseph Califano, UCSD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2020

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2029

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)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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