A Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract

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.

• Drug: Tadalafil
  20 mg once daily for 10 - 14 days
  Other Name: Cialis
• Other: Placebo Pill
  Placebo

• Placebo Comparator: Placebo
  Intervention: Other: Placebo Pill
• Experimental: Drug
  Tadalafil 20 mg once per day
  Intervention: Drug: Tadalafil

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