Overview

Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
This study will examine the combination of pembrolizumab and tadalafil for safety and efficacy in advanced head and neck cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of California, San Diego
Treatments:
Pembrolizumab
Tadalafil
Criteria
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).