Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx
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 Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Pilot Study of Phosphodioesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.|
- 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 [ 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. ] [ Designated as safety issue: No ]
- Optimal dosing schedule for tadalafil [ Time Frame: Analysis will be performed on patient tumor specimens obtained at the time of surgery ] [ Designated as safety issue: No ]
- Treatment-related side effects [ Time Frame: Side effects will be assessed via questionnaire at Day 5 and Day 20 of treatment ] [ Designated as safety issue: Yes ]
- Progression-free survival [ Time Frame: From the date of initiation of study treatment to the date of documented disease progression or death from any cause, whichever is earlier. ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the date of initiation of study treatment to date of death from any cause. ] [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Experimental: Arm B
Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Placebo Comparator: Arm C
Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.
- 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.
|United States, Florida|
|University of Miami Sylvester Comprehensive Cancer Center - Miami|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Donald T. Weed, MD||University of Miami Sylvester Comprehensive Cancer Center|