Head and Neck Squamous Cell Carcinoma
Conditions
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.
Interventions
DRUGTadalafil
20 mg once daily for 10 - 14 days
OTHERPlacebo Pill
Placebo
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
5 subjects were screen failures
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo Pill: Placebo | 15 |
| Tadalafil Tadalafil: 20 mg once daily for 10 - 14 days | 17 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Tadalafil |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 6 | 58 years STANDARD_DEVIATION 12 | 60 years STANDARD_DEVIATION 15 |
| Clinical stage Node (N) stage : N0/N1 | 7 Participants | 14 Participants | 7 Participants |
| Clinical stage Node (N) stage : N2/N3 | 8 Participants | 17 Participants | 9 Participants |
| Clinical stage Tumor (T) stage : T0/Tx/T1/T2 | 12 Participants | 18 Participants | 6 Participants |
| Clinical stage Tumor (T) stage : T3/T4 | 3 Participants | 13 Participants | 10 Participants |
| Ethanol (ETOH) Exposure Ever | 7 Participants | 17 Participants | 10 Participants |
| Ethanol (ETOH) Exposure Never | 6 Participants | 10 Participants | 4 Participants |
| Human Papilloma Virus (HPV) status Negative | 6 Participants | 16 Participants | 10 Participants |
| Human Papilloma Virus (HPV) status Positive | 8 Participants | 13 Participants | 5 Participants |
| Human Papilloma Virus (HPV) status Unknown | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/other | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 27 Participants | 14 Participants |
| Region of Enrollment United States | 15 Participants | 32 Participants | 17 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 16 Participants |
| Site of Squamous Cell Carcinoma Hypopharynx/larynx | 1 Participants | 7 Participants | 6 Participants |
| Site of Squamous Cell Carcinoma Oral cavity | 5 Participants | 7 Participants | 2 Participants |
| Site of Squamous Cell Carcinoma Oropharynx | 9 Participants | 15 Participants | 6 Participants |
| Site of Squamous Cell Carcinoma Unknown | 0 Participants | 3 Participants | 3 Participants |
| Tobacco exposure Ever | 7 Participants | 21 Participants | 14 Participants |
| Tobacco exposure Never | 8 Participants | 10 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 25 |
| other Total, other adverse events | 0 / 15 | 0 / 25 |
| serious Total, serious adverse events | 2 / 15 | 1 / 25 |
Outcome results
Primary
Change in Immune Response After Tadalafil Administration
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.
Time frame: Change from baseline to up to 14 days post-intervention
Population: Data was not evaluable in 1/15 participants from the placebo group, 2/17 participants in the tadalafil group (for T-cell expansion, CD4/CD69, CD/CD69) and 1/17 for DTH area.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change in Immune Response After Tadalafil Administration | T-cell expansion | 1.13 fold change |
| Placebo | Change in Immune Response After Tadalafil Administration | DTH area | 1.14 fold change |
| Placebo | Change in Immune Response After Tadalafil Administration | CD4/CD69 | 0.90 fold change |
| Placebo | Change in Immune Response After Tadalafil Administration | CD8/CD69 | 0.93 fold change |
| Tadalafil | Change in Immune Response After Tadalafil Administration | CD8/CD69 | 1.14 fold change |
| Tadalafil | Change in Immune Response After Tadalafil Administration | T-cell expansion | 1.59 fold change |
| Tadalafil | Change in Immune Response After Tadalafil Administration | CD4/CD69 | 1.29 fold change |
| Tadalafil | Change in Immune Response After Tadalafil Administration | DTH area | 4.74 fold change |