Evaluation of Intravenous Ferric Derisomaltose on Physical Capacity and Immunological Parameters in Non-Anemic Iron-Deficient Colorectal Cancer Patients

The primary objective of this study is to evaluate the **physical capacity** in patients with colorectal cancer following the infusion of iron or placebo. Additionally, the study aims to assess immunological changes in these patients by utilizing the Neutrophil to Lymphocyte Ratio (NLR) and Nanostring methodology. This investigation seeks to determine the effects of intravenously administered iron on both short- and long-term outcomes, as well as its impact on the tumor microenvironment. The clinical relevance of this study lies in its potential to enhance understanding of how iron supplementation may influence physical performance and immune response in non-anemic iron-deficient patients with colorectal cancer, potentially informing future therapeutic strategies.

The clinical trial involves participants diagnosed with **iron deficiency** and scheduled for curative intended elective colon or rectum cancer surgery. The study population includes both male and female subjects, aged 18 years and older, with a **hemoglobin** level greater than 7.0 mmol/L and either a serum ferritin level of 100 µg/L or less, or a transferrin saturation (TSAT) of 20% or less. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are selected based on their planned surgical intervention for colorectal cancer at UICC stage I-III. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effects of intravenously administered **iron** in non-anemic iron-deficient patients with colorectal cancer. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is set to commence recruitment on October 1, 2024, and is expected to conclude by May 1, 2026. The primary objective is to assess changes in physical capacity and immunological responses, specifically focusing on the Neutrophil to Lymphocyte Ratio (NLR) and immune function at the tumor's invasive front using Nanostring methodology.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as planned curative surgery for colorectal cancer, UICC stage I-III, age of 18 years or older, and specific hemoglobin and serum ferritin levels. Following the screening, participants will be randomly assigned to receive either the test product, **ferric derisomaltose**, or a placebo, **sodium chloride**, both administered via intravenous infusion. The maximum treatment period is one day, with a single dose of up to 1000 mg for the test product and 100 ml for the placebo.

Subsequent follow-up visits will monitor primary endpoints, including changes in cellular respiration and NLR, and secondary endpoints such as subjective physical capacity, adverse events, and survival rates. The end-of-study visit will conclude the participant's involvement, which is expected to last until the final follow-up assessments are completed. Participants may be withdrawn from the study early if they experience significant adverse events or if they no longer meet the inclusion criteria. The trial is categorized as a Phase 4 study, indicating it involves a drug already in routine medical use, and is not considered low-intervention due to its comprehensive evaluation of both short- and long-term outcomes.

The clinical trial involves the administration of two treatments, one of which is **sodium chloride**. The product, marketed under the name "Natriumchlorid 'Noridem'", is a **solution for injection**. It is utilized as a **solvent** for parenteral use and is administered via **intravenous infusion**. The maximum daily and total dose is 100 ml, with a treatment period limited to one day. Sodium chloride serves as the placebo in this study, providing a control for evaluating the effects of the experimental treatment.

The experimental treatment in this trial is **ferric derisomaltose**, marketed as "Monofer". This is a **solution for injection/infusion** and is also administered through **intravenous infusion**. The maximum daily and total dose for ferric derisomaltose is 1000 mg, with a treatment period of one day. Ferric derisomaltose is a polymer-based iron preparation used to assess its effects on physical capacity and immunological changes in patients with colorectal cancer. The study aims to evaluate the impact of intravenously administered iron on both short- and long-term outcomes, as well as its effects on the tumor microenvironment.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the impact of intravenously administered iron on patients with colorectal cancer. The primary endpoints include changes in cellular respiration, specifically **VO2max at the Anaerobic Threshold**, measured by the gold standard Cardio Pulmonary Exercise Testing (CPET). Additionally, the preoperative change in the **Neutrophil to Lymphocyte Ratio (NLR)** and the up and downregulation of immune function at the invasive front of the tumor, measured by the Nanostring™ PanCancer Immune® profiling panel, will be evaluated.

Secondary endpoints will focus on the patients' subjective description of physical capacity, assessed using the Fatigue Severity Score questionnaire. Treatment characteristics such as adverse events, serious adverse events, blood transfusions, and changes in transferrin, ferritin, transferrin saturation, iron, hemoglobin, and phosphate levels will also be monitored. Additional secondary endpoints include the length of hospital stay, infectious complications measured by the comprehensive complication index, and quality of recovery-15 during admission. Long-term outcomes such as one and five-year survival rates and recurrence rates will also be analyzed.