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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00894413
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 45
• Location: 1
• Arms: 2
• Actual Duration (Months): 57.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Tadalafil; Other: Placebo Pill	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract
• Actual Study Start Date: May 8, 2007
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Other: Placebo Pill; Placebo
Experimental: Tadalafil Tadalafil 20 mg once per day	Drug: Tadalafil; 20 mg once daily for 10 - 14 days; Other Names: Cialis

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts 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

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

2. 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.

3. 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.

1. 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

1. Current treatment with nitrates.

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

3. 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.

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

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

6. prior history of non-arterial ischemic optic retinopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joseph Califano, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00894413
• Other Study ID Numbers: J0813; 1R21CA135635-01; NA_00012749
• First Posted: May 7, 2009
• Last Update Posted: Jun 11, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Tadalafil

Study Results

Participant Flow

Pre-assignment Detail	5 subjects were screen failures

Arm/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo Pill: Placebo	Tadalafil: 20 mg once daily for 10 - 14 days
Period Title: Overall Study
STARTED	15	25
COMPLETED	15	17
NOT COMPLETED	0	8

Baseline Characteristics

Arm/Group Title	Placebo	Tadalafil	Total
Arm/Group Description	Placebo Pill: Placebo	Tadalafil: 20 mg once daily for 10 - 14 days	Total of all reporting groups
Overall Participants	15	17	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (6)	60 (15)	58 (12)
Sex: Female, Male (Count of Participants)
Female	2 13.3%	1 5.9%	3 9.4%
Male	13 86.7%	16 94.1%	29 90.6%
Race/Ethnicity, Customized (Count of Participants)
White	13 86.7%	14 82.4%	27 84.4%
Black/other	2 13.3%	3 17.6%	5 15.6%
Region of Enrollment (Count of Participants)
United States	15 100%	17 100%	32 100%
Tobacco exposure (Count of Participants)
Never	8 53.3%	2 11.8%	10 31.3%
Ever	7 46.7%	14 82.4%	21 65.6%
Ethanol (ETOH) Exposure (Count of Participants)
Never	6 40%	4 23.5%	10 31.3%
Ever	7 46.7%	10 58.8%	17 53.1%
Site of Squamous Cell Carcinoma (Count of Participants)
Hypopharynx/larynx	1 6.7%	6 35.3%	7 21.9%
Oral cavity	5 33.3%	2 11.8%	7 21.9%
Oropharynx	9 60%	6 35.3%	15 46.9%
Unknown	0 0%	3 17.6%	3 9.4%
Clinical stage (Count of Participants)
Tumor (T) stage : T0/Tx/T1/T2	12 80%	6 35.3%	18 56.3%
Tumor (T) stage : T3/T4	3 20%	10 58.8%	13 40.6%
Node (N) stage : N0/N1	7 46.7%	7 41.2%	14 43.8%
Node (N) stage : N2/N3	8 53.3%	9 52.9%	17 53.1%
Human Papilloma Virus (HPV) status (Count of Participants)
Negative	6 40%	10 58.8%	16 50%
Positive	8 53.3%	5 29.4%	13 40.6%
Unknown	1 6.7%	2 11.8%	3 9.4%

Outcome Measures

1. Primary Outcome

Title	Change in Immune Response After Tadalafil Administration
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Tadalafil
Arm/Group Description	Placebo Pill: Placebo	Tadalafil: 20 mg once daily for 10 - 14 days
Measure Participants	14	16
T-cell expansion	1.13	1.59
DTH area	1.14	4.74
CD4/CD69	0.90	1.29
CD8/CD69	0.93	1.14

Adverse Events

Time Frame	up to 4 years
Arm/Group Title	Placebo		Tadalafil
Arm/Group Description	Placebo Pill: Placebo		Tadalafil: 20 mg once daily for 10 - 14 days
All Cause Mortality
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/25 (0%)
Serious Adverse Events
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		1/25 (4%)
Gastrointestinal disorders
Chest Pain	1/15 (6.7%)	1	1/25 (4%)	1
General disorders
Fever	1/15 (6.7%)	1	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Tadalafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.