- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03993353
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Khushbu Singh
- Phone Number: (858) 246-2604
- Email: ksingh@health.ucsd.edu
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- Recruiting
- UCSD Moores Cancer Center
-
Contact:
- CTO
- Email: CancerCTO@ucsd.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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)
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:
10 mg by mouth daily
Other Names:
|
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
Investigators
- Principal Investigator: Joseph Califano, UCSD
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomatognathic Diseases
- Mouth Diseases
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Head and Neck Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Esophageal Neoplasms
- Mouth Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Pembrolizumab
- Tadalafil
Other Study ID Numbers
- 190098
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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