A Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Tadalafil; Placebo Pill
Intervention description: 20 mg once daily for 10 - 14 days; Placebo
Intervention MeSH terms: Tadalafil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      The purpose of this trial is to determine whether or not Cialis (tadalafil) administered to
      head and neck squamous cell cancer patients augments immune response.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed, previously untreated invasive head and neck squamous cell
             carcinoma OR histologically confirmed not yet treated recurrent head and neck squamous
             cell carcinoma (must be at least 3 months after diagnosis and completion of treatment
             for primary disease or last recurrence).

          2. Disease location amenable to biopsy in outpatient clinical setting or operative biopsy
             within routine accepted schedule and practice of clinical care

          3. No medical contraindication to biopsy of target lesion.

          4. ECOG performance status 0-1

          5. Required laboratory data (to be obtained within 4 weeks of initiation):

               -  Platelets > 75,000/mm³

               -  Calculated Creatinine Clearance (CRCL)> 60 mL/min iii. Total serum bilirubin <
                  1.5 mg/dL.

               -  No intercurrent illness likely to prevent protocol therapy or surgical resection

          6. Patients with a history of a curatively treated malignancy must be disease-free and
             have a survival prognosis that exceeds five years.

          7. Female patients must not be pregnant or breast feeding. A negative pregnancy test is
             required within 14 days of randomization for all women of childbearing potential.

          8. Willingness and ability to give signed written informed consent.

        Exclusion Criteria:

          1. Known severe hypersensitivity to tadalafil or any of the excipients of this product

          2. Patients who have a concurrent malignancy or a history of previous malignancy treated
             with curative therapy within the last 3 months (other than squamous/basal cell cancer
             of the skin or cervical cancer) who have a survival prognosis of < 5 years.

          3. Treatment with a non-approved or investigational drug within 30 days before day 1 of
             trial treatment.

          4. Incomplete healing from previous oncologic or other major surgery.

          5. Pregnancy or breast feeding (women of childbearing potential).

          6. As judged by the investigator, any evidence of severe or uncontrolled systemic disease
             (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).

          7. Evidence of any other significant clinical disorder or laboratory finding that makes
             it undesirable for the subject to participate in the trial.

          8. Current therapy with ketoconazole or oral antifungal therapy.

          9. History of significant hypotensive episode requiring hospitalization.

         10. A history of acute myocardial infarction within prior 3 months, uncontrolled angina,

         11. Uncontrolled arrhythmia, or uncontrolled congestive heart failure

         12. Age < 18

         13. History of any of the following cardiac conditions:

               -  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.

         14. 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 III as defined in Protocol Attachment
                  LVHG.3) within 6 months of planned tadalafil administration

         15. Current treatment with nitrates.

         16. Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such
             as ketoconazole or ritonavir.

         17. Received treatment within the last 30 days with a drug or device that has not received
             regulatory approval for any indication at the time of Visit 1.

         18. Prior chronic immune suppressive state (AIDS, immunosuppressive therapy).

         19. History of hypotension and/or blindness during prior treatment with Tadalafil or other
             PDE-5 inhibitors.

         20. prior history of non-arterial ischemic optic retinopathy