Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

NCT03993353 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 190098
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Keywords

cancer; pembrolizumab; tadalafil; cialis; opdivo; immunotherapy; metastatic; carcinoma; pd-1; pde

Outcome Measures

Primary Outcomes (2)

• Rate of Dose Limiting Toxicity (DLT)

  Rate of dose limiting toxicity at least possibly attributable to study treatment

  2 years

• Overall Survival (OS)

  Overall survival at 12 months post-enrollment

  12 months

Secondary Outcomes (3)

• Response Measured by RECIST 1.1

  12 months

• Progression Free Survival

  2 years

• Adverse Event Rates

  2 years

Study Arms (1)

Tadalafil and Pembrolizumab

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Tadalafil

Interventions

Pembrolizumab DRUG

200 mg intravenously every 3 weeks

Also known as: Keytruda

Tadalafil and Pembrolizumab

Tadalafil DRUG

10 mg by mouth daily

Also known as: Cialis

Tadalafil and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Esophageal Neoplasms; Neoplasm Metastasis; Mouth Neoplasms; Carcinoma; Parkinson Disease 4, Autosomal Dominant Lewy Body; Pyridoxine-dependent epilepsy

Interventions

pembrolizumab; Tadalafil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Joseph Califano
• Organization: University of California, San Diego

CancerCTO@health.ucsd.edu

(858) 822-5354

Study Officials

• Joseph Califano

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: April 7, 2020
• Primary Completion: April 16, 2022
• Study Completion: January 9, 2024
• Last Updated: February 12, 2026
• Results First Posted: February 12, 2026

Record last verified: 2026-01

Locations

US (1)