Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

NCT ID: NCT03993353

Last Updated: 2024-11-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-07
• Study Completion Date: 2029-03-01

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tadalafil and Pembrolizumab

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

200 mg intravenously every 3 weeks

Tadalafil

Intervention Type: DRUG

10 mg by mouth daily

Interventions

Pembrolizumab

200 mg intravenously every 3 weeks

Intervention Type: DRUG

Tadalafil

10 mg by mouth daily

Intervention Type: DRUG

Other Intervention Names

Keytruda; Cialis

Eligibility Criteria

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

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Joseph Califano

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Califano

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

UCSD Moores Cancer Center

La Jolla, California, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

190098

Identifier Type: -

Identifier Source: org_study_id