ImmunoNutrition and Colorectal Adenocarcinoma Surgery - INCAS Study

Study Overview
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Brief Summary
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Compared to upper gastrointestinal (GI) malignancies, CRC patients generally present with satisfactory nutritional status at surgery and malnutrition is typically present in advanced stages of CRC. Therefore, in the latter surgery may not be offered with curative intent. Based on the current evidence, the role of OIN appears to be consolidated for malnourished patients undergoing surgery for gastrointestinal cancer. Regarding not malnourished patients, there is still no clear correlation between OIN and decrease in post-operative complications. Furthermore, whether OIN increases immune response within the tumour microenvironment is based on studies with poor number of patients.

Detailed Description
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Randomized, controlled, open-label, single-centre study in patients candidate for elective curative surgery for colon-rectal cancer. The study intervention consists of the oral nutritional supplementation enriched with immune-nutrients delivered before and after surgery in addition to standard dietary advice according to E.R.A.S. protocol. All patients will follow low-fiber diet according to ERAS protocol during the study period. Patients assigned to the experimental arm will assume also Impact Oral®, an oral nutritional supplement with immune-nutrients (hyper-proteic formula), manufactured and commercialized by Nestlé Health Science S.p.a. It is a liquid drink packaged in a brick of 237 ml. Patients will assume Impact Oral® for 5 days before surgery and 5 day after surgery.

Official Title
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ImmunoNutrition and Colorectal Adenocarcinoma Surgery: a Randomized Study. INCAS Study

Conditions
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Colorectal Adenocarcinoma

Intervention / Treatment
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* Dietary Supplement: Impact Oral®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years or older; histologically confirmed adenocarcinoma of colon or rectum; Eligible for elective curative surgery with indication of colon and/or rectal resection in laparoscopy with mini-invasive technique; eligible for ERAS protocol; Written informed consent to the study participation according to the Local Ethic Committee requirements before any study procedure; Exclusion Criteria: colon or rectal resection for benign disease; TNM Stage ≥4; neoadjuvant radio and/or chemotherapy ASA score > 3; contraindications to oral nutrition (e.g. dysphagia, pyloric stenosis) or hypersensitivity to any ingredient of study product; albuminemia < 3.0 g/l; weight loss > 10% in the last 3-6 months; BMI < 18.5 kg/m2; pregnant or breastfeeding; Not self-sufficient or with poor family compliance; Congenital or acquired immunodeficiency; Active uncontrolled pre-operative infections or other clinically relevant concomitant illness that preclude laparoscopic procedure; Bowel obstruction or parenteral nutrition or gastric tube;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, open-label, single-centre study in patients candidate to elective curative surgery for colon-rectal cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (interventional arm)<br>a low-fiber dietary advice + oral nutritional supplement enriched with immune-nutrients for 5 pre-operative days and 5 post-operative days. | Dietary Supplement: Impact Oral®<br>* All patients will follow low-fiber diet according to ERAS protocol during the study period. Patients assigned to the experimental arm will assume also Impact Oral®, an oral nutritional supplement with immune-nutrients (hyper-proteic formula), manufactured and commercialized by Nestlé Health Science S.p.a. It is a liquid drink packaged in a brick of 237 ml. Patients will assume Impact Oral® for 5 days before surgery and 5 day after surgery.<br>|
| No Intervention: Arm B (control arm)<br>a low fiber dietary advice only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure - Number of patients with grade 2 or higher post-operative complications | Number of patients with grade 2 or higher post-operative complications according to Clavien-Dindo classification occurred within 30 days post-surgical intervention. | within 30 days post-surgical intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measure - Hospital length of stay | Hospital length of stay defined as hospitalization from the day of surgery until discharge | From the day of surgery until discharge, assessed up to 7 days | 
| Secondary Outcome Measure - Reoperation rate | Reoperation rate within 30 days from index surgery defined as any unplanned post-operative procedure including a return in the operating room or an imaging-guided intervention within 30 days following the index surgery | within 30 days following the index surgery | 
| Secondary Outcome Measure - Unplanned readmissions | Unplanned readmissions within 30 days from discharge | within 30 days from discharge | 
| Secondary Outcome Measure - 30-day mortality for any cause | 30-day mortality for any cause | 30-day mortality for any cause | 
| Secondary Outcome Measure - Safety assessed according to CTCAE | Safety assessed according to criteria to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5 | From admission to discharge, assessed up to 42 days | 
| Secondary Outcome Measure - Nutritional status before and after surgery | Nutritional status before and after surgery will be assessed evaluating albumin, prealbumin and transferrin serum levels: differences at day 1, 3, 5, 15 and 30 after surgery from T0 (7-10 days before surgery) will be calculated and compared between the two arms | differences at day 1, 3, 5, 15 and 30 after surgery from T0 (7-10 days before surgery) will be calculated and compared between the two arms | 
| Secondary Outcome Measure - Inflammatory status before and after surgery | Inflammatory status before and after surgery will be assessed evaluating leukocytes (x10^(9)/L), C-reactive protein (PCR) (mg/dL), procalcitonin (ug/L), neutrophil-lymphocyte (ratio), and lactate dehydrogenase (LDH) serum levels (U/L). The haematic quantification of this biomarkers provides information about the inflammatory status. | differences at day 1, 3, 5, 15 and 30 after surgery from T0 (7-10 days before surgery) will be calculated and compared between the two arms |