Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as tadalafil, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This randomized clinical trial is studying how well tadalafil works in treating patients who are undergoing surgery for cancer of the oral cavity or oropharynx.

Detailed Description
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OBJECTIVES: To analyze the phenotype and the function of the tumor-induced suppressive network associated with squamous cell carcinoma (SCC) of the head and neck in patients with SCC of the oral cavity or oropharynx treated with tadalafil followed by definitive surgical resection. To analyze the immune response before and after treatment with tadalafil to determine whether or not tadalafil treatment modulates in these patients. To compare two doses of tadalafil to determine whether there are measurable differences in immune response in these patients. To analyze treatment-related side effects of tadalafil at each of the two doses tested in these patients. OUTLINE: Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive oral tadalafil once daily on days 1-20 in the absence of unacceptable toxicity. Arm II: Patients receive oral tadalafil (at a higher dose than in arm I) once daily on days 1-20 in the absence of unacceptable toxicity. Arm III: Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity. All patients undergo scheduled definitive surgical resection on day 23. Patients undergo blood sample collection at baseline, on day 20, and at 6 weeks after surgical resection for correlative laboratory studies. Patients also undergo tumor tissue sample collection at baseline and at the time of surgical resection. Samples are analyzed for immunological markers by Fluorescence-activated cell sorting (FACS) and Immunohistochemistry (IHC). After completion of study treatment, patients are followed periodically for at least 3 years.

Official Title
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Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Tadalafil
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Patients with surgically resectable oral cavity SCC, all subsites, T1 - T4, N0 - N3 Patients with surgically resectable oropharyngeal SCC, all subsites, T1 - T2, N0 - N1 Patients with surgically resectable T4 oropharyngeal SCC, all subsites, N0 - N3 Patients must be 18 years old or older EXCLUSION CRITERIA: Patients with previous surgical resection, radiation, or chemotherapy will be excluded to rule out possible effects of local tissue changes secondary to previous treatment Patients with surgically unresectable disease at primary site or regional lymph nodes Patients with T1 - T2 SCC oropharynx, N2 - N3 Patients with T3 SCC oropharynx , N0 - N3 Any patient for whom non-surgical therapy is recommended as treatment of choice after multidisciplinary treatment evaluation Patients with an altered mental status or not capacitated for their medical decision making Patients with severe or unstable cardiac or cerebrovascular disease are excluded myocardial infarction within the last 90 days unstable angina or angina occurring during sexual intercourse New York Heart Association Class 2 or greater heart failure in the last 6 months uncontrolled arrhythmias hypotension (<90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg) stroke within the last 6 months Left ventricle outflow obstruction. Pregnant and nursing mothers will not be enrolled given unknown effects to offspring Concurrent nitrate, alpha-blocker, or cytochrome P-450 inhibitor use Renal Insufficiency defined as creatinine clearance less than 51. Creatinine clearance will be determined by the following Cockcroft-Gault Equation: (140-age) * (Wt in kg) * (0.85 if female) / (72 * Cr) Patients with hepatic insufficiency. Patients currently taking a Phosphodiesterase (PDE) inhibitors for erectile dysfunction Patients who are immunocompromised, for reasons not directly related to patients malignancy Patients with significant alcohol or drug abuse Patients with unilateral blindness, hereditary retinal disorders, or increased risk of blindness Patients with unilateral deafness, history of hearing loss, hearing aid dependence, or clinically evident hearing loss

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A - Tadalafil 10mg<br>Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity. | Drug: Tadalafil<br>* Given orally<br>* Other names: Cialis;|
| Experimental: Arm B - Tadalafil 20mg<br>Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity. | Drug: Tadalafil<br>* Given orally<br>* Other names: Cialis;|
| Placebo Comparator: Arm C - Placebo<br>Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity. | Other: Placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of MDSC Concentration in the Blood | Ratio of the number of Myeloid Derived Suppressor Cells (MDSC) in the Blood, per treatment group, from Baseline to End of Treatment at Time of Surgery. | Baseline, End of Treatment at time of Surgery | 
| Ratio of T-reg Cell Concentration in the Blood | Ratio of the number of regulatory T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery.. | Baseline, End of Treatment at Time of Surgery | 
| Ratio of Tumor-specific T-cell Concentration in the Blood | Ratio of the number of tumor specific T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery. | Baseline, End of Treatment at Time of Surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal Dosing Schedule for Tadalafil |  | Baseline, End of Treatment at Time of Surgery. | 
| Number of Participants Experiencing Adverse Events | Assessment of Treatment-related Side Effects. Number of participants experiencing adverse events | From Day 1 to Day 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage I verrucous carcinoma of the oral cavity, stage II verrucous carcinoma of the oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity