Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Donald T. Weed, University of Miami
ClinicalTrials.gov Identifier:
NCT00843635
First received: February 12, 2009
Last updated: July 25, 2014
Last verified: July 2014
  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 Phosphodioesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 42
Study Start Date: September 2008
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Drug: Tadalafil
Given orally
Experimental: Arm B
Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Drug: Tadalafil
Given orally
Placebo Comparator: Arm C
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 FACS and IHC.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
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 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
University of Miami
Investigators
Principal Investigator: Donald T. Weed, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

No publications provided

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
Last Updated: July 25, 2014
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
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 19, 2014