Neoplasms

All Conditions

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Influenza, Human

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

All Drugs and Chemicals

Vasodilator Agents

Urological Agents

Vaccines

Poly ICLC

Tadalafil

Immunologic Factors

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

The first 6 participants will be enrolled in the open label Phase I portion of the study and will receive Tadalafil, Anti-mucin 1 (MUC1) Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, placebo for the Anti-MUC1 Vaccine and placebo for the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive placebo for Tadalafil, the Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

For eligible participants who opt out of receiving study intervention. Participants in this group will receive SOC treatment only.

Tadalafil tablets administered by mouth. Dose will be between 10 to 20 mg adjusted depending on patient's body weight. On course 1, Tadalafil will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil will be administered daily for 14 consecutive days. No Tadalafil will be provided on Course 5.

300 uL Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-MUC1 Vaccine

300 uL Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-Influenza Vaccine

Placebo tablets mimicking Tadalafil administered by mouth. On course 1, Tadalafil Placebo will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil placebo will be administered daily for 14 consecutive days. No Tadalafil Placebo will be provided on Course 5.

Tadalafil Placebo

Placebo for Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Placebo for Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5..

Anti-MUC1 Vaccine Placebo

Treatment according to prescribed standard of care regimen.

Standard of Care Treatment

Placebo for Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Placebo for Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-Influenza Vaccine Placebo

Donald T Weed, MD, FACS

The investigators hypothesize that Tadalafil treatment, by lowering Myeloid Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs), can prime an antitumor immune response and promote a permissive environment that should increase the efficacy of anti-tumor vaccine in a setting of minimal residual disease.

This study is halting accrual at the end of the phase 1 portion of the study as data from the phase I study suggest that an alternative approach for the phase 2 portion of the study be undertaken. A newly designed Phase II trial is being developed and will be submitted as a new study protocol.

PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC

PDE5 Inhibition Via Tadalafil (Cialis®) to Enhance Anti-Tumor MUC1 Vaccine Efficacy in Patients With Resectable, and Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC): A Phase I/II Clinical Trial

The primary objective of the lead-in, open-label, single-arm, phase I part of study will evaluate the safety of Tadalafil in combination with anti-MUC1/anti-influenza vaccines (TV) in terms of adverse events (AEs), serious adverse events (SAEs) and treatment-limiting toxicities (TLTs).

The primary objective of phase II is to evaluate immune response (tumor-specific immune response of the anti- MUC1 and anti-influenza vaccines when combined with Tadalafil. Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by Enzyme-Linked ImmunoSpot (ELISPOT), specific Immunoglobulin G (IgG) concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.

Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by ELISPOT, specific IgG concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.

The rate of recurrence-free survival (RFS) in patients with recurrent or second primary HNSCC after salvage surgery. RFS is defined as the time from date of Surgery to the date of first documented recurrence. All patients will be rendered disease free (i.e. no measurable disease) after surgery, thus any confirmed evidence of disease recurrence regardless of size or site will constitute the recurrence time point. Recurrence will be demonstrated by clinical assessments such as clinical examinations and tumor assessments (possibly) by CT, PET/CT or MRI.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC	NCT02544880	Head and Neck S... Head and Neck C...	Tadalafil Anti-MUC1 Vacci... Anti-Influenza ... Tadalafil Place... Anti-MUC1 Vacci... Standard of Car... Anti-Influenza ...	18 Years -	University of Miami
PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC	NCT02544880	Head and Neck S... Head and Neck C...	Tadalafil Anti-MUC1 Vacci... Anti-Influenza ... Tadalafil Place... Anti-MUC1 Vacci... Standard of Car... Anti-Influenza ...	18 Years -	University of Miami

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