Targeting inflammation to reduce 90-day and 1-year postoperative severe morbidity in patients with unfavorable inflammatory profile undergoing oncologic surgery (POST-CARE trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To test the role of the experimental intervention, consisting of the combination of preoperative ketorolac and post-operative low-dose aspirin plus hypoglycemic diet in reducing 90-day postoperative morbidity.

Conditions and MedDRA coding

Patients scheduled for major surgery for oncologic indication

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age ≥ 18 years
2. Histologically documented cancer
3. Surgery performed for curative intent
4. High RBT index (≥18)
5. Patients scheduled for major surgical procedures (including thoracic, head and neck, abdominal (peritoneal/retroperitoneal), urogenital, and breast/reconstructive surgeries
6. Major surgery is defined according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes, according to the criteria proposed by Marin et al. in 2020
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Female participants must not be pregnant, not breastfeeding. Women of childbearing age must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment
9. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications
10. Adequate organ function: absolute neutrophil count ≥ 1,500/mm^3 platelet count ≥ 100,000/mm^3 hemoglobin ≥ 9 g/dl AST and ALT ≤ 1.5* times upper limit of normal (ULN) bilirubin ≤ 1.5* times ULN creatinine clearance ≥ 45 ml/min or serum creatinine ≤1.5 x ULN NOTE: * ≤ 3 times ULN if liver metastases are present
11. Ability of subject to understand and the willingness to sign a written informed consent document
12. Previous/ongoing aspirin therapy is not an exclusion criteria

Exclusion criteria 20

1. Patients undergoing palliative surgery
2. Patients undergoing neuro-surgical procedures
3. Patients with specific or nutritional dietary requirement (malnutrition or at high risk for malnutrition, sarcopenic or high risk to be sarcopenic)
4. Low body mass index (BMI<18.5kg/m2)
5. Have type 1 diabetes mellitus or type 2 diabetes mellitus treated with insulin or insulin secretagogues
6. Any post-surgical nutritional requirements (e.g., patients deserving to have parenteral nutrition after discharge will be excluded from the trial)
7. Any patient with a known predisposing history of a coagulation or platelet defect
8. Any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren’s, sarcoidosis etc.) detected at the time of screening.
9. Diagnosis of immunodeficiency or chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
10. Allogeneic tissue/solid organ transplant
11. Autologous/allogeneic stem cell transplantation
12. Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
13. Known hypersensitivity to active substances (ketorolac and aspirin) or any of their excipients including previous clinically significant hypersensitivity reaction to treatments.
14. Medical contraindication to non-steroidal anti-inflammatory drugs / aspirin administration
15. Known history of human immunodeficiency virus (HIV) infection and/or HIV-related Kaposi Sarcoma
16. Known history of or positivity for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
17. History of (non-infectious) pneumonitis that required steroids or current pneumonitis; history of active tuberculosis (Bacillus tuberculosis)
18. Clinically significant cardiovascular disease within 12 months of the first dose of study treatment including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
19. Prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment
20. Vaccination with live vaccine(s) within 30 days before the first dose of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. to test the efficacy of preoperative ketorolac followed by postoperative, dietary and pharmacologic glycemic/inflammatory control (through a combination of Mediterranean diet and low-dose aspirin) in reducing 90-day surgery-related morbidity (grade 3 or more according to the Clavain Dindo Classification) in high-risk patients (those with an RBT≥18) undergoing major surgical procedures

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical Trial Center

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical Trial Center

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications