Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx
September 25, 2015 updated by: Donald T. Weed
Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- University of Miami Sylvester Comprehensive Cancer Center - Miami
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 120 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm A - Tadalafil 10mg
Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
|
Given orally
Other Names:
|
|
Experimental: Arm B - Tadalafil 20mg
Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
|
Given orally
Other Names:
|
|
Placebo Comparator: Arm C - Placebo
Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.
|
Given orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Ratio of MDSC Concentration in the Blood
Time Frame: Baseline, End of Treatment at time of Surgery
|
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
Time Frame: Baseline, End of Treatment at Time of Surgery
|
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
Time Frame: Baseline, End of Treatment at Time of Surgery
|
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
Time Frame: Baseline, End of Treatment at Time of Surgery.
|
Baseline, End of Treatment at Time of Surgery.
|
|
|
Number of Participants Experiencing Adverse Events
Time Frame: From Day 1 to Day 20
|
Assessment of Treatment-related Side Effects.
Number of participants experiencing adverse events
|
From Day 1 to Day 20
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Donald T. Weed, MD, University of Miami Sylvester Comprehensive Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2008
Primary Completion (Actual)
April 1, 2015
Study Completion (Actual)
April 1, 2015
Study Registration Dates
First Submitted
February 12, 2009
First Submitted That Met QC Criteria
February 12, 2009
First Posted (Estimate)
February 13, 2009
Study Record Updates
Last Update Posted (Estimate)
October 19, 2015
Last Update Submitted That Met QC Criteria
September 25, 2015
Last Verified
September 1, 2015
More Information
Terms related to this study
Keywords
- stage III squamous cell carcinoma of the lip and oral cavity
- stage III verrucous carcinoma of the oral cavity
- stage IV squamous cell carcinoma of the lip and oral cavity
- stage IV verrucous carcinoma of the oral cavity
- stage III squamous cell carcinoma of the oropharynx
- stage IV squamous cell carcinoma of the oropharynx
- stage I squamous cell carcinoma of the lip and oral cavity
- stage II squamous cell carcinoma of the lip and oral cavity
- stage I squamous cell carcinoma of the oropharynx
- stage II squamous cell carcinoma of the oropharynx
- stage I verrucous carcinoma of the oral cavity
- stage II verrucous carcinoma of the oral cavity
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20070918
- SCCC-2008006 (Other Identifier: UM/Sylvester Comprehensive Cancer Center)
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