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


N/A
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

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Trial Information

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


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 FACS and IHC.

After completion of study treatment, patients are followed periodically for at least 3
years.

Inclusion Criteria


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 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Immune response as assessed by number of CD4+ and CD8+ cells in tumor tissue by IHC and proliferation of CD8+ lymphocytes in peripheral blood mononuclear cells by FACS

Outcome Time Frame:

The primary endpoint, patient immune response, will be assessed by several parameters quantifying the presence and function of MDSC and T cell populations at the time of surgery as compared to pre-treatment.

Safety Issue:

No

Principal Investigator

Donald T. Weed, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Miami Sylvester Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

EPROST-20070918

NCT ID:

NCT00843635

Start Date:

September 2008

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136