Description:
This study will examine the combination of pembrolizumab and tadalafil for safety and
efficacy in advanced head and neck cancer.
Title
- Brief Title: Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer
- Official Title: A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Clinical Trial IDs
- ORG STUDY ID:
190098
- NCT ID:
NCT03993353
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
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | Keytruda | Tadalafil and Pembrolizumab |
Tadalafil | Cialis | Tadalafil and Pembrolizumab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Tadalafil and Pembrolizumab | Experimental | Tadalafil for up to 12 months and pembrolizumab for up to 24 months. | |
Eligibility 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).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Rate of Dose Limiting Toxicity (DLT) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Rate of dose limiting toxicity at least possibly attributable to study treatment |
Secondary Outcome Measures
Measure: | Response measured by RECIST 1.1 |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Progression free survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Adverse event rates |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of California, San Diego |
Trial Keywords
- cancer
- pembrolizumab
- tadalafil
- cialis
- opdivo
- immunotherapy
- metastatic
- carcinoma
- pd-1
- pde
Last Updated
June 23, 2021