Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

Sponsor

University of California, San Diego (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03993353

Collaborator

(none)

Enrollment

Location

Arm

31.8

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Head and Neck Carcinoma Head and Neck Cancer Stage III Head and Neck Cancer Stage IV Head and Neck Cancer Metastatic Cancer Cancer of Esophagus Cancer, Metastatic Cancer of Head and Neck Cancer of Mouth Cancer of Neck	Drug: Pembrolizumab Drug: Tadalafil	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Actual Study Start Date :

Apr 7, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil and Pembrolizumab Tadalafil for up to 12 months and pembrolizumab for up to 24 months.	Drug: Pembrolizumab 200 mg intravenously every 3 weeks Other Names: Keytruda Drug: Tadalafil 10 mg by mouth daily Other Names: Cialis

Arm

Intervention/Treatment

Experimental: Tadalafil and Pembrolizumab

Tadalafil for up to 12 months and pembrolizumab for up to 24 months.

Drug: Pembrolizumab

200 mg intravenously every 3 weeks

Other Names:

Keytruda

Drug: Tadalafil

10 mg by mouth daily

Other Names:

Cialis

Outcome Measures

Primary Outcome Measures

Rate of Dose Limiting Toxicity (DLT) [2 years]
Rate of dose limiting toxicity at least possibly attributable to study treatment
Overall Survival (OS) [12 months]
Overall survival at 12 months post-enrollment

Secondary Outcome Measures

Response measured by RECIST 1.1 [12 months]
Progression free survival [2 years]
Adverse event rates [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).