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

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

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.

Trial Description

Primary Outcome:

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

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).

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.

View this trial on ClinicalTrials.gov