A Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract

Phase 2

Completed

• Conditions: Head and Neck Squamous Cell Carcinoma
• Interventions: Other: Placebo Pill; Drug: Tadalafil

• Registration Number: NCT00894413
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

The purpose of this trial is to determine whether or not Cialis (tadalafil) administered to head and neck squamous cell cancer patients augments immune response.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-08
• Study First Submitted: 2009-05-05
• Study First Submitted QC: 2009-05-06
• Study First Posted: 2009-05-07
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Status Verified: 2019-05
• Results First Submitted: 2019-05-22
• Results First Submitted QC: 2019-05-22
• Last Update Submitted: 2019-05-22
• Results First Posted: 2019-06-11
• Last Update Posted: 2019-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Histologically confirmed, previously untreated invasive head and neck squamous cell carcinoma OR histologically confirmed not yet treated recurrent head and neck squamous cell carcinoma (must be at least 3 months after diagnosis and completion of treatment for primary disease or last recurrence).

2. Disease location amenable to biopsy in outpatient clinical setting or operative biopsy within routine accepted schedule and practice of clinical care

3. No medical contraindication to biopsy of target lesion.

4. ECOG performance status 0-1

5. Required laboratory data (to be obtained within 4 weeks of initiation):

   • Platelets > 75,000/mm³
   • Calculated Creatinine Clearance (CRCL)> 60 mL/min iii. Total serum bilirubin < 1.5 mg/dL.
   • No intercurrent illness likely to prevent protocol therapy or surgical resection

6. Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds five years.

7. Female patients must not be pregnant or breast feeding. A negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.

8. Willingness and ability to give signed written informed consent.

Exclusion Criteria

1. Known severe hypersensitivity to tadalafil or any of the excipients of this product

2. Patients who have a concurrent malignancy or a history of previous malignancy treated with curative therapy within the last 3 months (other than squamous/basal cell cancer of the skin or cervical cancer) who have a survival prognosis of < 5 years.

3. Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment.

4. Incomplete healing from previous oncologic or other major surgery.

5. Pregnancy or breast feeding (women of childbearing potential).

6. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).

7. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.

8. Current therapy with ketoconazole or oral antifungal therapy.

9. History of significant hypotensive episode requiring hospitalization.

10. A history of acute myocardial infarction within prior 3 months, uncontrolled angina,

11. Uncontrolled arrhythmia, or uncontrolled congestive heart failure

12. Age < 18

13. History of any of the following cardiac conditions:

    • Angina requiring treatment with long-acting nitrates.
    • Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration.
    • Unstable angina within 90 days of visit 1 (Braunwald 1989).
    • Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention.

14. History of any of the following coronary conditions within 90 days of planned tadalafil administration:

    • Myocardial Infarction.
    • Coronary artery bypass graft surgery.
    • Percutaneous coronary intervention (for example, angioplasty or stent placement).
    • Any evidence of heart disease (NYHA≥Class III as defined in Protocol Attachment LVHG.3) within 6 months of planned tadalafil administration

15. Current treatment with nitrates.

16. Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir.

17. Received treatment within the last 30 days with a drug or device that has not received regulatory approval for any indication at the time of Visit 1.

18. Prior chronic immune suppressive state (AIDS, immunosuppressive therapy).

19. History of hypotension and/or blindness during prior treatment with Tadalafil or other PDE-5 inhibitors.

20. prior history of non-arterial ischemic optic retinopathy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Pill	-
Tadalafil	Tadalafil	Tadalafil 20 mg once per day

Primary Outcome Measures

Name	Time	Method
Change in Immune Response After Tadalafil Administration	Change from baseline to up to 14 days post-intervention	Median fold-change in immune response of T-cell expansion, delayed-type hypersensitivity reactions, CD4/CD69, CD8/CD69. A positive value indicates an increase in immune response.

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States