Abdominal CancerPhase 1PERIOP-04NCT02998736
Trial of Perioperative Tadalafil and Influenza Vaccination in Cancer Patients Undergoing Major Surgical Resection of a Primary Abdominal Malignancy
A Phase 1 study testing Cialis and Influenza vaccine in people with Abdominal Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Abdominal Cancer
- What is being tested?
- Cialis and Influenza vaccine
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- 21 Nov 2017to 1 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
- Active infection of any site requiring ongoing treatment.
- Known anatomical deformities of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or any condition that might predispose the patient to priapism.
- History of Guillaine-Barré Syndrome.
- Subjects with a medical or psychological impediment to probable compliance with the protocol should be excluded.
- Active drug or alcohol use or dependence or other conditions that, in the opinion of the investigator, would interfere with adherence to study requirements. Social alcohol use is acceptable.
- Concurrent inhibitors of moderate or strong CYP3A4 inhibitors
- Taking any other PDE-5 inhibitor (such as sildenafil) during the active phase of the study between enrollment to SD35.
- History of lactose or milk sugar intolerance
- Liver or Kidney disease
- Sickle cell anemia
- Peptic ulcer or other bleeding disorders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PERIOP-04 Phase Ib Trial of Perioperative Tadalafil and Influenza Vaccination in Cancer Patients Undergoing Major Surgical Resection of a Primary Abdominal Malignancy
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.
Read the detailed description
Surgical resection of a primary malignancy, while critical for cure, results in postoperative immune suppression, characterized by MDSC mediated inhibition of NK cell killing. In preclinical models the causal link between this immune suppression and the formation of postoperative metastases is undeniable. Fortunately, this postoperative immune suppression is preventable using modulators of MDSC and NK cell function. In this Phase Ib study the hypothesis is that simultaneous administration of perioperative tadalafil, to prevent MDSCs from suppressing NK cells, and influenza vaccine, to directly activate NK cells will safely and effectively reverse the effects of surgical stress on NK cell cytotoxicity. This is a necessary first step towards demonstrating that this re-purposed perioperative regimen can reduce the formation of postoperative metastatic disease in cancer surgery patients.
In this proposed Phase I trial a carefully selected promising perioperative immunomodulatory regimen, which includes tadalafil and influenza vaccination, for rapid clinical translation. The proposal is to re-purpose these drugs, they already have ample safety data associated with their use but neither agent has been systematically administered immediately prior to surgery. This trial will allow us to not only establish the safety of this regimen but will permit a rigorous assessment of its ability to reverse surgery-induced suppression of NK cells. If this regimen can effectively prevent postoperative NK cell dysfunction without any regimen limiting toxicity then this will provide the necessary data required to undertake a randomized efficacy study in a specific cancer subtype, with cancer recurrence as the primary endpoint.
- Conditions
- Abdominal Cancer
- Being tested
- Cialis, Influenza vaccine
- Keywords
- Colon
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CialisDrug
Also called Tadalafil
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
Influenza vaccineBiological
Also called Agriflu
One 0.5mL intramuscular injection the day of surgery
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Cialis; Biological: Influenza vaccine |
| Control | No intervention | No intervention in the perioperative period |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the change in the number of regimen limiting toxicities (RLT) in the experimental cohort
Adverse events, vitals and medications will be collected.
Measured: 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: 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: measured on day 1, 3, 7, 10 and 35 post surgery blood specimens
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study start21 Nov 2017
- Primary completion1 Sep 2022
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Abdominal CancerStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rebecca Auer, Doctor, Principal investigator, The Ottawa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02998736
- Sponsor's protocol ID
- 20160855-01H
- Acronym
- PERIOP-04
- Status last verified
- Dec 2022
- First submitted
- 6 Dec 2016
- Last updated
- 28 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40237463
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PERIOP-04 Phase Ib Trial of Perioperative Tadalafil and Influenza Vaccination in Cancer Patients Undergoing Major Surgical Resection of a Primary Abdominal Malignancy
- ClinicalTrials.gov ID
- NCT02998736
- Acronym / sponsor ID
- PERIOP-04 / 20160855-01H
- Conditions
- Abdominal Cancer
- Keywords
- Colon
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 21 Nov 2017 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Surgical resection of a primary malignancy, while critical for cure, results in postoperative immune suppression, characterized by MDSC mediated inhibition of NK cell killing. In preclinical models the causal link between this immune suppression and the formation of postoperative metastases is undeniable. Fortunately, this postoperative immune suppression is preventable using modulators of MDSC and NK cell function. In this Phase Ib study the hypothesis is that simultaneous administration of perioperative tadalafil, to prevent MDSCs from suppressing NK cells, and influenza vaccine, to directly activate NK cells will safely and effectively reverse the effects of surgical stress on NK cell cytotoxicity. This is a necessary first step towards demonstrating that this re-purposed perioperative regimen can reduce the formation of postoperative metastatic disease in cancer surgery patients.
In this proposed Phase I trial a carefully selected promising perioperative immunomodulatory regimen, which includes tadalafil and influenza vaccination, for rapid clinical translation. The proposal is to re-purpose these drugs, they already have ample safety data associated with their use but neither agent has been systematically administered immediately prior to surgery. This trial will allow us to not only establish the safety of this regimen but will permit a rigorous assessment of its ability to reverse surgery-induced suppression of NK cells. If this regimen can effectively prevent postoperative NK cell dysfunction without any regimen limiting toxicity then this will provide the necessary data required to undertake a randomized efficacy study in a specific cancer subtype, with cancer recurrence as the primary endpoint.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Cialis, Biological: Influenza vaccineCialis 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 |
| Control | No intervention | –No intervention in the perioperative period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (26 listed)
- 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®.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CialisAlso: TadalafilCialis 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 | Intervention |
| Influenza vaccineAlso: AgrifluOne 0.5mL intramuscular injection the day of surgery | Biological | Intervention |
Primary outcome
Determine the change in the number of regimen limiting toxicities (RLT) in the experimental cohort
Time frame: measured at day 1, 3, 7, 10 and 35 post surgery
Adverse events, vitals and medications will be collected.
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.
Time frame: measured at day 1, 3, 7, 10 and 35 post surgery
Adverse events reported
1 secondary outcome
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).
Time frame: measured on day 1, 3, 7, 10 and 35 post surgery blood specimens
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2022.
- Derived from this study: PubMed 40237463Hirsch 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rebecca Auer, Doctor principal investigator
The Ottawa Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cialis and Influenza vaccine in people with Abdominal Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the change in the number of regimen limiting toxicities (RLT) in the experimental cohort (time frame: measured at day 1, 3, 7, 10 and 35 post surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02998736, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2022.