Clinical trial NCT00843635: Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx
Official title: Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2009-02-13
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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 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

Primary outcomes:
measure: Ratio of MDSC Concentration in the Blood
timeFrame: Baseline, End of Treatment at time of Surgery
measure: Ratio of T-reg Cell Concentration in the Blood
timeFrame: Baseline, End of Treatment at Time of Surgery
measure: Ratio of Tumor-specific T-cell Concentration in the Blood
timeFrame: Baseline, End of Treatment at Time of Surgery
Secondary outcomes:
measure: Optimal Dosing Schedule for Tadalafil
timeFrame: Baseline, End of Treatment at Time of Surgery.
measure: Number of Participants Experiencing Adverse Events
timeFrame: From Day 1 to Day 20
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Donald T. Weed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, Nazarian R, Califano J, Borrello I, Serafini P. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015 Jan 1;21(1):39-48. doi: 10.1158/1078-0432.CCR-14-1711. Epub 2014 Oct 15.