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

Exclusion Criteria

• •1. Medical contraindication to biopsy of target lesion
• •2. Intercurrent illness likely to prevent protocol therapy or conventional planned therapy
• •3. Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater
• •4. Known severe hypersensitivity to tadalafil or any of the excipients of this product
• •5. Current treatment with nitrates
• •6. Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir
• •7. History of hypotension and/or blindness during prior treatment with tadalafil or other PDE5 inhibitors
• •8. Prior history of non-arterial ischemic optic retinopathy
• •9. Prior adverse reaction to diphtheria vaccine
• •10. Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.
• •11. 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), for which the survival prognosis is \< 5 years
• •12. Treatment with a non-approved or investigational drug within 30 days before visit 1
• •13. Incomplete healing from previous oncologic or other major surgery
• •14. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• •15. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial
• •16. History of significant hypotensive episode requiring hospitalization
• •17. History of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure
• •18. History of any of the following cardiac conditions:
• •I. Angina requiring treatment with long-acting nitrates II. Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration III. Unstable angina within 90 days of visit 1 (Braunwald 1989) IV. Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention
• •19. History of any of the following coronary conditions within 90 days of planned tadalafil administration:
• •I. Myocardial Infarction II. Coronary artery bypass graft surgery III. Percutaneous coronary intervention (for example, angioplasty or stent placement) IV. Any evidence of heart disease (NYHA≥Class III as defined in Protocol Attachment LVHG.3) within 6 months of planned tadalafil administration
• •20. Prior chronic immune suppressive state (AIDS, immunosuppressive therapy)