Clinical Trials /

Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

NCT03993353

Description:

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

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
PembrolizumabKeytrudaTadalafil and Pembrolizumab
TadalafilCialisTadalafil 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

NameTypeDescriptionInterventions
Tadalafil and PembrolizumabExperimentalTadalafil for up to 12 months and pembrolizumab for up to 24 months.
  • Pembrolizumab
  • Tadalafil

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

April 15, 2020