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

NCT ID: NCT00843635

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2015-04-30

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A - Tadalafil 10mg

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

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

Given orally

Arm B - Tadalafil 20mg

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

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

Given orally

Arm C - Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Given orally

Interventions

Tadalafil

Given orally

Intervention Type: DRUG

Placebo

Given orally

Intervention Type: OTHER

Other Intervention Names

Cialis

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Donald T. Weed

OTHER

Sponsor Role: lead

Responsible Party

Donald T. Weed

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Donald T. Weed, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami Sylvester Comprehensive Cancer Center

Locations

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25320361 (View on PubMed)

Other Identifiers

SCCC-2008006

Identifier Type: OTHER

Identifier Source: secondary_id

20070918

Identifier Type: -

Identifier Source: org_study_id