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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tadalafil
Placebo
Sponsored by
Donald T. Weed
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm A - Tadalafil 10mg

Arm B - Tadalafil 20mg

Arm C - Placebo

Arm Description

Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.

Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.

Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.

Outcomes

Primary Outcome Measures

Ratio of MDSC Concentration in the Blood
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
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
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
Number of Participants Experiencing Adverse Events
Assessment of Treatment-related Side Effects. Number of participants experiencing adverse events

Full Information

First Posted
February 12, 2009
Last Updated
September 25, 2015
Sponsor
Donald T. Weed
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1. Study Identification

Unique Protocol Identification Number
NCT00843635
Brief Title
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

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Donald T. Weed

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A - Tadalafil 10mg
Arm Type
Experimental
Arm Description
Patients will receive 10mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Arm Title
Arm B - Tadalafil 20mg
Arm Type
Experimental
Arm Description
Patients will receive 20mg/day Tadalafil orally on days 1 - 20 in the absence of unacceptable toxicity.
Arm Title
Arm C - Placebo
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo once daily on days 1-20 in the absence of unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Tadalafil
Other Intervention Name(s)
Cialis
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Ratio of MDSC Concentration in the Blood
Description
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.
Time Frame
Baseline, End of Treatment at time of Surgery
Title
Ratio of T-reg Cell Concentration in the Blood
Description
Ratio of the number of regulatory T cells in the blood, per treatment group, from Baseline to End of Treatment at Time of Surgery..
Time Frame
Baseline, End of Treatment at Time of Surgery
Title
Ratio of Tumor-specific T-cell Concentration in the Blood
Description
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.
Time Frame
Baseline, End of Treatment at Time of Surgery
Secondary Outcome Measure Information:
Title
Optimal Dosing Schedule for Tadalafil
Time Frame
Baseline, End of Treatment at Time of Surgery.
Title
Number of Participants Experiencing Adverse Events
Description
Assessment of Treatment-related Side Effects. Number of participants experiencing adverse events
Time Frame
From Day 1 to Day 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald T. Weed, MD
Organizational Affiliation
University of Miami Sylvester Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Sylvester Comprehensive Cancer Center - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25320361
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.
Results Reference
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Tadalafil in Treating Patients Undergoing Surgery for Cancer of the Oral Cavity or Oropharynx

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