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

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ClinicalTrials.gov Identifier: NCT01697800
Recruitment Status : Unknown
Verified May 2014 by Sidney Kimmel Comprehensive Cancer Center.
Recruitment status was:  Recruiting
First Posted : October 2, 2012
Last Update Posted : May 13, 2014
National Institute of Dental and Craniofacial Research (NIDCR)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

Brief Summary:

Head and neck squamous cell carcinoma (HNSCC) is a lethal solid malignancy with 5 year survival estimates of approximately 50%, and is associated with a high rate of systemic immune impairment as well as evasion of a tumor specific immune response. Preclinical and clinical data have shown that PDE5 inhibitors (tadalafil) can be used to augment immune function in HNSCC patients through inhibition of the cancer-induced myeloid derived suppressor cells (MDSCs).

A multi site phase II, randomized, prospective, biomarker endpoint trial to determine optimum timing and design of PDE5 antitumor immunotherapy (tadalafil) in conjunction with conventional therapy for HNSCC.

40 patients with biopsy proven HNSCC will be randomized to receive tadalafil (n=25) or placebo (n=15) for at least 10-14 days before starting conventional therapy and continuing until 90 days after completion of conventional therapy. Tumor-specific T cell responses will be assessed using HNSCC cell lines, in blood collected before initiation of tadalafil/placebo and at 60 and 90 days after completion of conventional therapy. Number and function of MDSC and Treg cells will be assessed before and at 60 and 90 days after completion of conventional therapy. Prevnar 13® vaccine will be administered 10-14 days after commencing tadalafil/placebo (before conventional therapy begins) and again at 60 days after completion of conventional therapy. Vaccine-specific responses assessed at 60 and 90 days post-conventional therapy will be used to measure the ability of tadalafil to augment immune response to vaccine.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Tadalafil Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract
Study Start Date : September 2012
Estimated Primary Completion Date : September 2014
Estimated Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Tadalafil
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo Capsules
Drug: Placebo
Active Comparator: Tadalafil
Drug: Tadalafil
Other Name: Cialis

Primary Outcome Measures :
  1. Increase in immune response after tadalafil administration [ Time Frame: 120-150 Days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥21 years
  2. 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). Patients may have local Stage I or II, or locoregionally advanced HNSCC Stage III or IV of the oral cavity, oropharynx, larynx, hypopharynx, or unknown primary, but no metastatic disease; Intent to treat with primary radiotherapy +/-chemotherapy
  3. Disease location amenable to biopsy in outpatient clinical setting or operative biopsy within routine accepted schedule and practice of clinical care
  4. ECOG performance status 0-1
  5. Required laboratory data (to be obtained within 2 weeks of initiation):

    • Platelets > 75,000/mm³
    • Calculated Creatinine Clearance (CRCL)> 60 mL/min
    • Total serum bilirubin < 1.5 mg/dL
  6. Willingness and ability to give signed written informed consent.

Exclusion Criteria:

  1. Medical contraindication to biopsy of target lesion
  2. Intercurrent illness likely to prevent protocol therapy or conventional planned therapy
  3. Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater
  4. Known severe hypersensitivity to tadalafil or any of the excipients of this product
  5. Current treatment with nitrates
  6. Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir
  7. History of hypotension and/or blindness during prior treatment with tadalafil or other PDE-5 inhibitors
  8. Prior history of non-arterial ischemic optic retinopathy
  9. Prior adverse reaction to diphtheria vaccine
  10. Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.
  11. 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), for which the survival prognosis is < 5 years
  12. Treatment with a non-approved or investigational drug within 30 days before visit 1
  13. Incomplete healing from previous oncologic or other major surgery
  14. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
  15. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial
  16. History of significant hypotensive episode requiring hospitalization
  17. History of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure
  18. History of any of the following cardiac conditions:

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

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

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01697800

United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21231
Contact: Zubair Khan, M.D., MPH    410-955-3157    zkhan@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Institute of Dental and Craniofacial Research (NIDCR)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01697800     History of Changes
Other Study ID Numbers: J1247
2P50DE019032 ( U.S. NIH Grant/Contract )
NA_00073880 ( Other Identifier: JHMIRB )
First Posted: October 2, 2012    Key Record Dates
Last Update Posted: May 13, 2014
Last Verified: May 2014

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents