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Checkpoint Inhibitor

Tadalafil + Pembrolizumab for Head and Neck Cancer

Phase 2
Recruiting
Led By Joseph Califano
Research Sponsored by University of California, San Diego
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Patients must have normal organ and marrow function
Patients (at least 18 years of age) must have recurrent or metastatic squamous cell carcinoma of the head and neck
Must not have
Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent)
Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater within 3 months of trial enrollment
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 2 years
Awards & highlights

Summary

This trial will test a combination of two drugs, pembrolizumab and tadalafil, to treat advanced head and neck cancer. The goal is to see if this combination is safe and more effective than using pembrolizumab alone. Pembrolizumab helps the immune system attack cancer by blocking a specific protein, while tadalafil helps by blocking another pathway. This approach aims to strengthen the immune system's ability to fight cancer. Pembrolizumab has been approved by the FDA for various cancers and has shown significant activity in treating advanced head and neck cancer.

Who is the study for?
Adults with recurrent or metastatic head and neck squamous cell carcinoma who have not used PD-1 or PD-L1 inhibitors in this setting, nor had certain heart conditions, autoimmune diseases, severe drug allergies, organ transplants, or are pregnant. They must have a life expectancy over 12 weeks and normal organ/marrow function.
What is being tested?
The trial is testing the safety and effectiveness of combining two drugs: pembrolizumab (an immunotherapy) and tadalafil (a medication originally for erectile dysfunction), to treat advanced head and neck cancer.
What are the potential side effects?
Possible side effects include immune-related reactions like inflammation in various organs, fatigue, skin rash; as well as headaches, indigestion from tadalafil. Serious cardiac events could occur due to pre-existing conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My organs and bone marrow are functioning normally.
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I am 18 or older with recurrent or metastatic squamous cell carcinoma of the head and neck.
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My cancer can be measured by tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I am not on strong immune system suppressing drugs.
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I have used tadalafil or similar medications daily for at least a month in the past 3 months.
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I have had a condition where my eye's optic nerve was damaged due to poor blood supply.
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I am currently taking a strong medication that affects liver enzymes.
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I have a heart condition that blocks blood flow from my heart.
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I am currently taking medication that stimulates guanylate cyclase.
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I have had an organ transplant.
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I have not had a stroke in the last 6 months.
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I am currently using long-acting PDE5 inhibitors.
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I take medication for chest pain.
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I have a family history of retinal disorders like retinitis pigmentosa.
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I have not had a heart attack or uncontrolled heart issues in the last 3 months.
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I am currently taking nitrates for my condition.
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I have been treated with PD-1 or PD-L1 inhibitors for recurrent or metastatic cancer.
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I had a positive heart stress test without any effective heart treatment afterwards.
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I have a history of HIV or active hepatitis B or C.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~2 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Overall Survival (OS)
Rate of Dose Limiting Toxicity (DLT)

Side effects data

From 2017 Phase 4 trial • 635 Patients • NCT02224846
9%
Viral upper respiratory tract infection
3%
Periodontitis
3%
Prostatitis
2%
Alanine aminotransferase increased
2%
Upper respiratory tract infection
2%
Abdominal pain upper
2%
Chronic gastritis
2%
Blood uric acid increased
2%
Insomnia
1%
Pharyngitis
1%
Sleep disorder
1%
Rhinitis
1%
Enteritis
1%
Eczema
1%
Rhinitis allergic
1%
Influenza
1%
Diabetes mellitus
1%
Gout
1%
Back pain
1%
Gastritis
1%
Urinary tract infection
1%
Dizziness
1%
Epistaxis
1%
Renal cyst
1%
Gastric polyps
1%
Gastrooesophageal reflux disease
1%
Nephrolithiasis
1%
Hypertension
1%
Pyrexia
1%
Large intestine polyp
1%
Abdominal distension
1%
Abdominal pain
1%
Dental caries
1%
Diarrhoea
1%
Gamma-glutamyltransferase increased
1%
Headache
1%
Cough
100%
80%
60%
40%
20%
0%
Study treatment Arm
2.5 mg/5 mg Tadalafil
5 mg Tadalafil

Trial Design

1Treatment groups
Experimental Treatment
Group I: Tadalafil and PembrolizumabExperimental Treatment2 Interventions
Tadalafil for up to 12 months and pembrolizumab for up to 24 months.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Pembrolizumab
FDA approved
Tadalafil
FDA approved

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
The most common treatments for Head and Neck Cancers (HNC) include PD-1 inhibitors and PDE5 inhibitors. PD-1 inhibitors, such as Pembrolizumab, block the PD-1 receptor on T-cells, preventing cancer cells from evading the immune system and enhancing the body's ability to detect and destroy cancer cells. PDE5 inhibitors, like Tadalafil, can modulate the immune environment by increasing blood flow and potentially enhancing the delivery of immune cells to the tumor site. These mechanisms are important for HNC patients as they offer potential improvements in immune response and targeted cancer treatment.
Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.Immunotherapy for head and neck squamous cell carcinoma.The genetic landscape of programmed death ligand-1 (PD-L1) alterations in head and neck cancer.

Find a Location

Who is running the clinical trial?

University of California, San DiegoLead Sponsor
1,169 Previous Clinical Trials
1,571,967 Total Patients Enrolled
Joseph Califano4.711 ReviewsPrincipal Investigator - UCSD
University of California, San Diego
5Patient Review
He is an excellent doctor and surgeon. I am an anaplastic thyroid cancer patient and he saved my life.

Media Library

Pembrolizumab (Checkpoint Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03993353 — Phase 2
Head and Neck Cancers Research Study Groups: Tadalafil and Pembrolizumab
Head and Neck Cancers Clinical Trial 2023: Pembrolizumab Highlights & Side Effects. Trial Name: NCT03993353 — Phase 2
Pembrolizumab (Checkpoint Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03993353 — Phase 2
~1 spots leftby Mar 2026