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

NCT01697800 | Completed Phase 2 Results DMC

• 3 other identifiers: J12472P50DE019032NA_00073880
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 phosphodiesterase 5 (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.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Change in Immune Response After Tadalafil Administration

  Baseline and 120-150 Days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients received placebo capsules for 2 weeks prior to standard of care treatment and continued for 3 months post standard of care treatment

Drug: Placebo

Tadalafil

ACTIVE COMPARATOR

Patients received 20 mg tadalafil capsules for 2 weeks prior to standard of care treatment and continued for 3 months post standard of care treatment

Drug: Tadalafil

Interventions

Tadalafil DRUG

Also known as: Cialis

Tadalafil

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥21 years
• 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
• Disease location amenable to biopsy in outpatient clinical setting or operative biopsy within routine accepted schedule and practice of clinical care
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• 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
• Willingness and ability to give signed written informed consent.

You may not qualify if:

• Medical contraindication to biopsy of target lesion
• Intercurrent illness likely to prevent protocol therapy or conventional planned therapy
• Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater
• Known severe hypersensitivity to tadalafil or any of the excipients of this product
• Current treatment with nitrates
• Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir
• History of hypotension and/or blindness during prior treatment with tadalafil or other PDE5 inhibitors
• Prior history of non-arterial ischemic optic retinopathy
• Prior adverse reaction to diphtheria vaccine
• Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.
• 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
• Treatment with a non-approved or investigational drug within 30 days before visit 1
• Incomplete healing from previous oncologic or other major surgery
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• Guo T, Califano JA. Molecular biology and immunology of head and neck cancer. Surg Oncol Clin N Am. 2015 Jul;24(3):397-407. doi: 10.1016/j.soc.2015.03.002. Epub 2015 Apr 20.

  PMID: 25979390 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Zubair Khan
• Organization: Johns Hopkins Medicine

zkhan@jhmi.edu

410-955-3157

Study Officials

• Zubair Khan, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: October 2, 2012
• Study Start: September 1, 2012
• Primary Completion: July 14, 2014
• Study Completion: July 14, 2014
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-02

Locations

US (1)