Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

  • End date
    Dec 24, 2022
  • participants needed
  • sponsor
    University of California, San Diego
Updated on 24 January 2021
measurable disease
squamous cell carcinoma
primary cancer
head and neck cancer
neck cancer
advanced head and neck carcinoma
metastatic head and neck cancer
metastatic squamous cell carcinoma
advanced head and neck cancer


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


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.

Condition Oral Neoplasm, Cancer, Esophageal Diseases, Esophageal Cancer, head and neck cancer, Cancer/Tumors, Esophageal Carcinoma, Squamous Cell Carcinoma of the Head and Neck, Head and Neck Squamous Cell Carcinoma, Ewing's Family Tumors, Squamous Cell Carcinoma of Head and Neck, Head and Neck Carcinoma, Head and Neck Cancer Metastatic, Carcinoma of the Head and Neck, Cancer (Pediatric), Esophageal Disorders, Oral Cavity Cancer, Neoplasms, Oral Cancer, Metastatic Head and Neck Cancer, Cancer Metastatic, Head and Neck Cancer Stage III, Head and Neck Cancer Stage IV, neck cancer, primary cancer, primary malignant neoplasm, malignancy, cancers, malignancies, malignant tumor, malignant tumors, esophagus cancer, oesophageal cancer, cancer of the head and neck, oral cancers, cancers metastatic, cancer of the esophagus, oesophageal carcinoma
Treatment Pembrolizumab, Tadalafil
Clinical Study IdentifierNCT03993353
SponsorUniversity of California, San Diego
Last Modified on24 January 2021


Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Cancer (Pediatric) or Oral Cancer or Head and Neck Cancer Metastatic or Head and Neck Cancer Stage IV or Cancer Metastatic or Cancer/Tumors or Oral Ne...?
Do you have any of these conditions: malignancy or Head and Neck Squamous Cell Carcinoma or Metastatic Head and Neck Cancer or Ewing's Family Tumors or malignant tumors or Esophageal Dise...?
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

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)
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Phone Email

Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note