Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx - Full Text View

Purpose

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.

Condition	Intervention
Head and Neck Cancer	Drug: Tadalafil Other: Placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Tadalafil

U.S. FDA Resources

Further study details as provided by University of Miami:

Primary Outcome Measures:

Ratio of MDSC Concentration in the Blood [ Time Frame: Baseline, End of Treatment at time of Surgery ] [ Designated as safety issue: No ]
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.
Ratio of T-reg Cell Concentration in the Blood [ Time Frame: Baseline, End of Treatment at Time of Surgery ] [ Designated as safety issue: No ]
Ratio of the number of regulatory T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery..
Ratio of Tumor-specific T-cell Concentration in the Blood [ Time Frame: Baseline, End of Treatment at Time of Surgery ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Optimal Dosing Schedule for Tadalafil [ Time Frame: Baseline, End of Treatment at Time of Surgery. ] [ Designated as safety issue: No ]
Number of Participants Experiencing Adverse Events [ Time Frame: From Day 1 to Day 20 ] [ Designated as safety issue: Yes ]
Assessment of Treatment-related Side Effects. Number of participants experiencing adverse events


Enrollment:	35
Study Start Date:	September 2008
Study Completion Date:	April 2015
Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A - Tadalafil 10mg Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.	Drug: Tadalafil Given orally Other Name: Cialis
Experimental: Arm B - Tadalafil 20mg Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.	Drug: Tadalafil Given orally Other Name: Cialis
Placebo Comparator: Arm C - Placebo Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.	Other: Placebo Given orally

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


Ages Eligible for Study:	18 Years to 120 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00843635

Locations


United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136

Sponsors and Collaborators

Donald T. Weed

Investigators


Principal Investigator:	Donald T. Weed, MD	University of Miami Sylvester Comprehensive Cancer Center

More Information

Publications:

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.


Responsible Party:	Donald T. Weed, Professor, University of Miami
ClinicalTrials.gov Identifier:	NCT00843635 History of Changes
Other Study ID Numbers:	20070918 SCCC-2008006
Study First Received:	February 12, 2009
Results First Received:	June 3, 2015
Last Updated:	September 25, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:


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

Additional relevant MeSH terms:


Carcinoma, Squamous Cell Head and Neck Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Neoplasms by Site	Tadalafil Phosphodiesterase 5 Inhibitors Vasodilator Agents Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Urological Agents

ClinicalTrials.gov processed this record on September 30, 2016