Trial of Perioperative Tadalafil and Influenza Vaccination in Cancer Patients Undergoing Major Surgical Resection of a Primary Abdominal Malignancy

NCT02998736 | Completed Phase 1 DMC

• 1 other identifier: 20160855-01H
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if giving Cialis for 5 days prior to surgery, on the day of surgery along with the influenza vaccine and Cialis 10 days after surgery will have an affect at the cell level for decreasing the chances of the spread of disease post surgery.

Conditions

Abdominal Cancer

Keywords

Colon

Outcome Measures

Primary Outcomes (2)

• Determine the change in the number of regimen limiting toxicities (RLT) in the experimental cohort

  Adverse events, vitals and medications will be collected.

  measured at day 1, 3, 7, 10 and 35 post surgery

• Document the change in the number and severity of CTCAE adverse events that are probably or definitely related to study treatment (tadalafil or influenza) in the experimental cohort.

  Adverse events reported

  measured at day 1, 3, 7, 10 and 35 post surgery

Secondary Outcomes (1)

• Compare the reduction in Natural Killer cell killing as measured on PBMC collected on SD1 as compared to baseline between the control and experimental cohorts, using a standard Natural Killer cell killing assay (51Chromium release assay).

  measured on day 1, 3, 7, 10 and 35 post surgery blood specimens

Study Arms (2)

Intervention

EXPERIMENTAL

Cialis 20 mg daily by mouth for 16 day. 5 days prior to surgery, day of surgery and 10 days post surgery. Influenza vaccine 0.5mL day of surgery

Drug: Cialis; Biological: Influenza vaccine

Control

NO INTERVENTION

No intervention in the perioperative period

Interventions

Cialis DRUG

Cialis 20 mg daily by mouth for 16 day. 5 days prior to surgery, day of surgery and 10 days post surgery. Influenza vaccine 0.5mL day of surgery

Also known as: Tadalafil

Intervention

Influenza vaccine BIOLOGICAL

One 0.5mL intramuscular injection the day of surgery

Also known as: Agriflu

Intervention

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of a primary abdominal malignancy consented to undergo major surgery with a planned length of stay of 3 or more days.
• Eligible patients must have signed a consent for surgical resection of the malignancy.
• Adequate hematological function defined as: platelet count ≥ 100 x 109/L, absolute neutrophil count ≥ 1 x 109/L, white blood count ≥ 2.5 x 109/L, hemoglobin count ≥ 90 g/L.
• Adequate organ functioning, including: total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST, ALT \< 2.5 x ULN; INR \<1.5 ; CrCl\>30mL/min.
• If sexually active, and of childbearing potential, subjects must agree to use acceptable birth control from screening until the final study visit (study day, SD35) or early termination. Acceptable methods of birth control include: spermicide with condom, diaphragm, or cervical cap, IUD (intrauterine device), hormonal contraception, vasectomy, and abstinence. (Plan B or the rhythm method are not considered reliable methods.
• Male subjects should agree to avoid having sex for 5 days before surgery and 10 days post surgery taking tadalafil due to the risk of sustained erection
• Ability to understand and provide a signed informed consent form (ICF) approved by the Institutional Review Board (IRB/IEC/REB).
• Ability to comply with protocol requirements.

You may not qualify if:

• Prior adjuvant chemotherapy or radiation within 8 weeks of planned surgery.
• Pregnant or nursing mothers or women of childbearing potential not using acceptable methods of birth control.
• Documented significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids, azathioprine, cyclosporin A). Subjects may be on physiologic doses of replacement prednisone or equivalent doses of corticosteroid (\<7.5 mg daily).
• History of autoimmune disease (even if controlled with medication) such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
• Allergies or any contraindication to the use of tadalafil or any components of Cialis® or the influenza vaccine (including eggs), Agriflu®.
• Serious intercurrent chronic or acute illness, or other illness considered by the investigator as an unwarranted high risk for an investigational product.
• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
• Patients with resting hypotension (BP \<90/50 at rest) or hypertension (BP \>170/110 at rest).
• Patients with cardiac failure or coronary artery disease causing unstable angina.
• Use any type of nitrate drug therapy, including short-acting nitrate-containing medications, due to the risk of developing potentially life-threatening hypotension. The use of organic nitrates, either regularly and/or intermittently, in any form (e.g. oral, sublingual, transdermal, by inhalation) is absolutely contraindicated (see list Appendix II).
• Use of guanylate cyclase stimulators (cinaciguat or riociguat).
• Use of alpha-blocker therapy (see list in Appendix I).
• Previous episode of non-arteritic anterior ischaemic optic neuropathy (NAION) or history of retinitis pigmentosa.
• Use of anti-platelet (excluding ASA) or anti-coagulation medication (Patients who discontinue such medications at least 7 days prior to first treatment may be eligible for this study).
• Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (at least 7 days prior to the first treatment), and PEG-IFN (at least14 days prior to the first treatment).

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (1)

• Hirsch C, Zorger AM, Baumann M, Park YS, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with solid tumours. Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015551. doi: 10.1002/14651858.CD015551.pub2.

  PMID: 40237463 DERIVED

MeSH Terms

Interventions

Tadalafil; Influenza Vaccines

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; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Rebecca Auer, Doctor

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 20, 2016
• Study Start: November 21, 2017
• Primary Completion: September 1, 2022
• Study Completion: October 1, 2022
• Last Updated: December 28, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)