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

Inclusion Criteria

• 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).
• Disease location amenable to biopsy in outpatient clinical setting or operative biopsy within routine accepted schedule and practice of clinical care
• No medical contraindication to biopsy of target lesion.
• ECOG performance status 0-1
• 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
• Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds five years.
• 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.
• Willingness and ability to give signed written informed consent.

Exclusion Criteria

• Known severe hypersensitivity to tadalafil or any of the excipients of this product
• 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.
• Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment.
• Incomplete healing from previous oncologic or other major surgery.
• Pregnancy or breast feeding (women of childbearing potential).
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.
• Current therapy with ketoconazole or oral antifungal therapy.
• History of significant hypotensive episode requiring hospitalization.
• A history of acute myocardial infarction within prior 3 months, uncontrolled angina,
• Uncontrolled arrhythmia, or uncontrolled congestive heart failure
• Age < 18
• 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.
• 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
• Current treatment with nitrates.
• Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir.
• 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.
• Prior chronic immune suppressive state (AIDS, immunosuppressive therapy).
• History of hypotension and/or blindness during prior treatment with Tadalafil or other PDE-5 inhibitors.
• prior history of non-arterial ischemic optic retinopathy