Immunosurveillance for Metastatic Colorectal Cancer (ISMCC)

The Role of Neutrophil Mitochondrial Dysfunction in Medical Rehabilitation During Palliative Chemotherapy for Metastatic Colorectal Cancer

The goal of this study type: clinical trial is to primary purpose: e.g., learn if intervention or health behavior can treat, prevent, diagnose etc. and improve the quality of life and reduce one-year mortality in palliative treatment of metastatic forms of colorectal cancer.. The main question[s] it aims to answer [is/are]:

1. Does the combination of sodium adenosine nucleonate and FOLFOX course affect chemotherapy efficacy and treatment adherence?
2. which of the assays can be considered a marker of the efficacy of the combination of sodium nucleonate and FOLFOX?

3. Effect of the combination of adenosine nucleonate sodium and FOLFOX on patient quality of life?

   • If there is a comparison group:_ Researchers will compare [compare the two arms of the main arm 100 patients and the control arm 100 patients] to see if [insert effects].

Participants will [describe the main tasks participants will be asked to do, interventions they'll be given and use bullets if it is more than 2 items].

1. To evaluate the efficacy of palliative care with 4 courses of FOLFOX-based chemotherapy combined with sodium nucleonate for metastatic colorectal cancer (CRC) in the main group.
2. In the control group in metastatic colorectal cancer to study the efficacy of 4 courses of stand-alone standard chemotherapy according to the FOLFOX scheme.
3. To examine the obtained results and compare the quality of life, dynamics of laboratory tests and overall survival in the main and control groups.
4. To evaluate the influence of quantitative and qualitative indices of mitochondrial activity in the blood of patients in the main and control groups.
5. To reveal the correlation between the dynamics of mitochondrial dysfunction, quality of life of patients, tolerance to toxic effects of chemotherapy, as well as the reduction of one-year mortality in patients with colorectal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Monitoring, Immunologic
• Intervention / Treatment: Biological: Placebo; Dietary supplement: Adenorine; Drug: FOLFOX regimen

Detailed Description

Materials and methods of the study. According to the approved by the Local Ethical Committee of the Kazakh National Medical University, it was planned to include in the study 200 patients from 19 regions of Kazakhstan with histological, verified diagnosis of "colorectal cancer", treated in oncological centers of 4 regions of Kazakhstan, where there were University Clinics.

Distribution of Colorectal Cancer Patients (CRC) by Type of Treatment.

1. Main group - Chemotherapy according to the FOLFOX regimen in combination with sodium nucleonate 100
2. Control group Chemotherapy according to the FOLFOX regimen 100 Study Design The study design included an evaluation of the effectiveness of FOLFOX chemotherapy in combination with sodium nucleinate immunotherapy in 187 patients with metastatic colorectal cancer at stages T3-4 N1-2 M1. Randomization into two groups-main and control-was performed using the envelope method.

The main group included 89 patients with metastatic colorectal cancer (stages T3-4 N1-2 M), receiving four courses of FOLFOX chemotherapy combined with mitochondrial immunotherapy using sodium nucleinate. The medical rehabilitation protocol involved administering sodium nucleinate at 50 mg per day: 25 mg in the morning and 25 mg at lunch before meals, daily for four months.

The control group consisted of 98 patients with metastatic colorectal cancer (stages T3-4 N1-2 M), who received only four courses of FOLFOX chemotherapy. In both groups, general and biochemical blood analyses were conducted monthly.

Additionally, before the start of treatment and one month after the end of treatment, PET-CT scans were performed, levels of tumour markers CEA and CA-19-9 were determined, immunological status CD4/CD8 and mitochondrial activity of neutrophils were assessed, and echocardiography was conducted to determine the left ventricular ejection fraction. A well-being questionnaire (the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29) was also administered.

Critical Points

1. Reduction in treatment interruptions due to leukopenia, neutropenia, and infectious complications during chemotherapy for metastatic colorectal cancer (CRC).
2. Increased percentage of tumour process stabilization during palliative chemotherapy for CRC.

Reduction in one-year mortality during palliative treatment of metastatic CRC. Statistical analysis of the study results was performed using the application program package "Statistica 7.0" for Windows (StatSoft, USA). The Mann-Whitney U-criterion was used to compare the studied samples by qualitative indicators.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Kazakhstan
  • Almaty, Kazakhstan, 050038
    • MIPOClinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Oncological patients with a histologically confirmed diagnosis of "colorectal cancer" and regional metastases at stages T1-4 N1-2 M0, who have provided informed consent to participate in the study.
2. Oncological patients with a histologically confirmed diagnosis of "colorectal cancer" with distant metastases at stages T1-4 N1-2 M1, who have provided informed consent to participate in the study.

Exclusion Criteria:

1. Oncological patients with a histologically confirmed diagnosis of "colorectal cancer" and regional metastases at stages T1-4 N1-2 M1, who have active forms of pulmonary tuberculosis, decompensated diabetes, decompensated cardiac, vascular, lung, liver, and renal failure.
2. Oncological patients with a histologically confirmed diagnosis of "colorectal cancer" with regional and distant metastases at stages T1-4 N1-2 M1, who have not provided informed consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy according to the FOLFOX regimen in combination with sodium nucleonate; Рatients with metastatic colorectal cancer (stages T3-4 N1-2 M), receiving four courses of FOLFOX chemotherapy (Day 1-2: Oxaliplatin 100 mg/m2 IV infusion, given as a 120 minutes IV infusion in 500 mL D5W, concurrent with leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2) IV infusion, followed by 5-FU 400 mg/m2 IV bolus, followed by 46-hour 5-FU infusion (2400 mg/m2 for first two cycles, and may be increased to 3000 mg/m2 if tolerated by patient (no toxicity > grade 1 during the first two cycles), days 3-14: Rest days) combined with mitochondrial immunotherapy using sodium nucleinate. The medical rehabilitation protocol involved administering sodium nucleinate at 50 mg per day: 25 mg in the morning and 25 mg at lunch before meals, daily for four months.	Dietary supplement: Adenorine; The immunostimulating effect of the drug is associated with its ability to activate the cells of the monocyte-macrophage system, thus increasing the functional activity of all parts of the body, stimulating the repair and regeneration of cells and tissues. It reduces the symptoms of the iflammatory process, stimulates the development of granulations and growth of epithelial tissues, accelerates the process of cleansing and healing of infected wounds. While with healthy people, it can be used as a phylactic drug that improves immunity protection. It was proved that when the drug is used externally, activation of macrophages occurs, thus accelerating wound cleansing process and stimulating reparative processes. In cases when thermal injury to the skin is more than 15-20% of the surface, there is a "stress syndrome" that suppresses the immune system. When exposed to DNA-Na, lymphocyte activation occurs, wound cleansing processes are accelerated.; Other Names: natural oligodeoxynucleotide; sodium nucleinate; Drug: FOLFOX regimen; (Day 1-2: Oxaliplatin 100 mg/m2 IV infusion, given as a 120 minutes IV infusion in 500 mL D5W, concurrent with leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2) IV infusion, followed by 5-FU 400 mg/m2 IV bolus, followed by 46-hour 5-FU infusion (2400 mg/m2 for first two cycles, and may be increased to 3000 mg/m2 if tolerated by patient (no toxicity > grade 1 during the first two cycles), days 3-14: Rest days)
Sham Comparator: Chemotherapy according to the FOLFOX regimen; Рatients with metastatic colorectal cancer (stages T3-4 N1-2 M), who received only four courses of FOLFOX chemotherapy (Day 1-2: Oxaliplatin 100 mg/m2 IV infusion, given as a 120 minutes IV infusion in 500 mL D5W, concurrent with leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2) IV infusion, followed by 5-FU 400 mg/m2 IV bolus, followed by 46-hour 5-FU infusion (2400 mg/m2 for first two cycles, and may be increased to 3000 mg/m2 if tolerated by patient (no toxicity > grade 1 during the first two cycles), days 3-14: Rest days). In both groups, general and biochemical blood analyses were conducted monthly	Biological: Placebo; Placebo; Drug: FOLFOX regimen; (Day 1-2: Oxaliplatin 100 mg/m2 IV infusion, given as a 120 minutes IV infusion in 500 mL D5W, concurrent with leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2) IV infusion, followed by 5-FU 400 mg/m2 IV bolus, followed by 46-hour 5-FU infusion (2400 mg/m2 for first two cycles, and may be increased to 3000 mg/m2 if tolerated by patient (no toxicity > grade 1 during the first two cycles), days 3-14: Rest days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EORTC QLQ-CR29	the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 max242 min59. whether higher scores mean a worse outcome	before the start of treatment and one month after the end of treatment
Dynamics of mitochondrial activity neutrophils	Mitochondrial dynamics refers to the changing process of fission, fusion, mitophagy and transport, which is crucial for optimal function in signal transduction and metabolism. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular fate, and a range of diseases, including neurodegenerative disorders, metabolic diseases, cardiovascular diseases and cancers. Herein, we review the mechanism of mitochondrial dynamics, and its impacts on cellular function. the normal range of cell distribution 30-60% 30% of the 200 cells counted. whether higher scores mean a better outcome.	before the start of treatment and one month after the end of treatment
Positron emission tomography/computed tomography	Positron emission tomography (PET/CT) is used prior to surgery in patients with metastatic or recurrent colorectal cancer to identify those with potentially curable disease or to dynamically monitor the course of the disease. normally, it does not accumulate an isotope. whether higher scores mean a worse outcome.	before the start of treatment and one month after the end of treatment
CEA	Carcinoembryonic Antigen Oncomarker is used in the diagnosis of malignant and benign tumors of GI organs or to dynamically monitor the course of the disease. normal concentration min=0 ng/ml max=5,5 ng/ml. whether higher scores mean a worse outcome.	before the start of treatment and one month after the end of treatment
CA 19-9 (Carbohydrate (carbohydrate) antigen 19-9)	CA 19-9 was discovered in the early 1980s by researchers working to identify tumor antigens in colorectal cancer or to dynamically monitor the course of the disease. normal concentration min=0 U/ml, max=27,0 U/ml. whether higher scores mean a worse outcome.	before the start of treatment and one month after the end of treatment
CD4/ CD8 ratio	Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer. The normal range of CD4+/CD8+ is from 1.0 to 4.0. the ratio level above and below the norm is considered a bad prognostic sign	before the start of treatment and one month after the end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiography with determination of left ventricular ejection fraction	Echocardiography with determination of left ventricular ejection fraction to detect impaired function of vital organs as a factor of exclusion from the study group. in the case of a violation of the vital function of the heart below normal parameters, it is a negative sign and the patient is subject to exclusion from the study.	before the start of treatment

Collaborators and Investigators

• Sponsor: MIPO Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): July 25, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: July 6, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Rehabilitation; Chemotherapy; Colorectal Cancer; Mitochondria; Sodium Nucleinate
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Anti-Ulcer Agents; Interferon Inducers; Sodium nucleinate
• Other Study ID Numbers: 3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No