Skip to main content
OpenTrials
Completed

NCT Number: NCT06509880

Immunosurveillance for Metastatic Colorectal Cancer

The goal of this clinical trial is to learn if adding sodium nucleinate to FOLFOX chemotherapy helps people with metastatic colorectal cancer (colon or rectal cancer that has spread). Researchers will also look at side effects and how people feel during treatment.

The main questions this study aims to answer are:

1. Does adding sodium nucleinate help treatment work better? 2. Does it improve quality of life (how people feel and function day to day)? 3. Does it affect survival at one year?

Researchers will compare:

1. FOLFOX chemotherapy plus sodium nucleinate versus 2. FOLFOX chemotherapy alone

Participants will:

1. Be randomly assigned (like flipping a coin) to one of the two groups; 2. Receive four cycles of FOLFOX chemotherapy; 3. Take sodium nucleinate daily if assigned to that group; 4. Have checkups and blood tests during the study (including tumor marker blood tests such as CEA and CA 19-9); 5. Complete quality-of-life questionnaires and have other planned tests that look at immune cells and how certain blood cells work; 6. Be followed after treatment to see how they are doing, including up to one year after starting the study.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Monitoring, Immunologic Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

40 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

MIPOClinic

Almaty, 050038, Kazakhstan

About this study

This randomized, single-blinded, parallel-group clinical trial was approved by the Local Ethics Committee of Kazakh National Medical University and conducted at oncology centers affiliated with university clinics in four regions of Kazakhstan. Participants had histologically confirmed metastatic colorectal cancer (T3-4 N1-2 M1). A total of 200 individuals were screened; 187 were enrolled and randomized.

Participants were allocated in a 1:1 ratio using sealed envelopes to receive either (1) FOLFOX chemotherapy plus sodium nucleinate or (2) FOLFOX chemotherapy alone. The intervention group received sodium nucleinate 50 mg per day (25 mg in the morning and 25 mg at lunch), starting 1 week before the first chemotherapy cycle and continued daily for 4 months. Both groups received four cycles of FOLFOX per institutional protocols.

Assessments included monthly clinical evaluation with general and biochemical blood tests during treatment. The following were assessed at baseline and at 1 month after completion of chemotherapy (approximately 5 months after baseline): FDG PET/CT, serum tumor markers (CEA and CA 19-9), peripheral blood immunologic status (CD4+/CD8+ ratio), and neutrophil mitochondrial activity (percentage of neutrophils with preserved mitochondrial function among 200 counted neutrophils). Baseline transthoracic echocardiography was performed to determine left ventricular ejection fraction. Health-related quality of life was assessed using the EORTC QLQ-C30 at baseline, post-treatment, and 1 year post-baseline.

Analyses were performed using Statistica 7.0 (StatSoft, USA). Continuous outcomes were compared between groups using the Mann-Whitney U test as specified in the protocol.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed colorectal cancer.
  • Locally advanced or metastatic disease as treated with palliative FOLFOX per protocol (including metastatic disease [M1]).
  • Able to receive FOLFOX chemotherapy and to comply with study procedures.
  • Provided written informed consent.

Exclusion criteria

  • Active pulmonary tuberculosis.
  • Decompensated diabetes mellitus.
  • Decompensated cardiac, vascular, pulmonary, hepatic, or renal failure.

Treatment and study plan

Adenorine

Dietary Supplement

Sodium nucleinate (Adenorine) is an immunomodulatory oligonucleotide preparation. In this trial, it was administered orally at 50 mg per day (25 mg in the morning and 25 mg at lunch before meals) for four months, starting 7 days before the first cycle of FOLFOX chemotherapy.

Other names: natural oligodeoxynucleotide, sodium nucleinate

Placebo

Other

Matching placebo administered orally (25 mg morning, 25 mg lunch) for four months, identical in appearance, taste, and packaging to sodium nucleinate. Contains microcrystalline cellulose.

FOLFOX regimen

Drug

(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)

Primary outcomes

  1. Relative Dose Intensity of FOLFOX

    Time frame: 1-4 cycles of FOLFOX

    Relative Dose Intensity (RDI) over cycles 1-4 of FOLFOX, calculated as (delivered dose intensity / planned dose intensity) × 100. Dose intensity accounts for both dose reductions and treatment delays for oxaliplatin (mg/m²/week) and infusional 5-fluorouracil (mg/m²/week).

Secondary outcomes

  1. EORTC QLQ-C30 Global Health Status/QoL (GHS/QoL)

    Time frame: Baseline (before start of chemotherapy); 1 month after completion of 4 cycles (approximately 5 months after baseline); 1 year post-baseline

    Global health status/quality of life subscale from the EORTC QLQ-C30. Scores are linearly transformed to a 0-100 scale. Higher scores indicate better global health status/quality of life (better outcome). Minimum = 0, maximum = 100. This is a subscale score, not a total scale score.

  2. Mitochondrial Activity of Neutrophils

    Time frame: Baseline (before start of chemotherapy) and post-treatment assessment 1 month after completion of chemotherapy

    Mitochondrial activity of neutrophils assessed in peripheral blood as the percentage (%) of neutrophils with preserved mitochondrial function among 200 counted neutrophils per participant. Range 0-100%. Higher percentages indicate better preserved neutrophil mitochondrial function. Primary metric: change from baseline to 1 month after completion of chemotherapy.

  3. Positron Emission Tomography/Computed Tomography (PET/CT) Tumour Metabolic Activity

    Time frame: Baseline (before start of chemotherapy) and follow-up FDG-PET/CT 1 month after completion of chemotherapy (approximately 5 months after baseline).

    Metabolic response to treatment assessed by [18F]FDG PET/CT using EORTC PET response criteria based on the change in tumor FDG uptake (e.g., SUV metric) between baseline and follow-up. Participants were classified into mutually exclusive categories: partial metabolic response (PMR) (≥25% decrease in tumor FDG uptake), stable metabolic disease (SMD) (does not meet PMR or PMD), or progressive metabolic disease (PMD) (≥25% increase in tumor FDG uptake and/or new FDG-avid lesions). Higher metabolic activity and PMD indicate worse disease activity.

  4. CEA Response (≥50% Decrease From Baseline)

    Time frame: Baseline (before start of chemotherapy) and 1 month after completion of chemotherapy (approximately 5 months after baseline)

    Serum CEA concentration measured in peripheral blood and reported in ng/mL. Higher CEA values generally indicate higher tumor burden and are used to monitor treatment response in conjunction with imaging. CEA response defined as a ≥50% decrease in serum CEA concentration from baseline to 1 month after completion of chemotherapy.

  5. CA 19-9(Carbohydrate Antigen 19-9) Response (≥50% Decrease From Baseline)

    Time frame: Baseline (before start of chemotherapy) and 1 month after completion of chemotherapy (approximately 5 months after baseline)

    CA 19-9 response defined as a ≥50% decrease in serum CA 19-9 concentration from baseline to 1 month after completion of chemotherapy. CA 19-9 measured in U/mL. Higher CA 19-9 values indicate higher tumor burden (worse outcome). Normal range approximately 0-27 U/mL.

  6. CD4+/CD8+ T-Cell Ratio (Peripheral Blood)

    Time frame: Baseline (before start of chemotherapy) and 1 month after completion of chemotherapy (approximately 5 months after baseline)

    CD4+/CD8+ T-cell ratio measured in peripheral blood (unitless ratio). The prespecified metric is the change in CD4+/CD8+ ratio from baseline to 1 month after completion of chemotherapy.

  7. Left Ventricular Ejection Fraction (LVEF) by Echocardiography

    Time frame: baseline (before start of chemotherapy)

    Left ventricular ejection fraction (LVEF) ≥50% by echocardiography at baseline was required for study inclusion. Patients with LVEF <50% were excluded.

Sponsors and collaborators

Lead sponsor

MIPO Clinic

Other

Registry information

Official study title

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

Acronym: ISMCC

Important dates

Study start
2022
Primary completion
2023
Study completion
2024
First posted
Jul 19, 2024
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.