A Clinical Study of Arfolitixorin in Patients With mCRC

Sponsor
Isofol Medical AB
Study ID
NCT06922383
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Metastatic Colorectal Cancer (mCRC)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Arfolitixorin — DRUG
    Every 14 days during treatment phase, antibody treatment (bevacizumab 5 mg/kg or cetuximab 500 mg/m² or panitumumab 6 mg/kg) will be administered as an i.v. infusion, followed by oxaliplatin 85 mg/m² or irinotecan 180 mg/m² administered as an i.v. infusion, and arfolitixorin administred as an i.v. infusion, followed by 5-FU administered as a 400 mg/m² i.v. bolus + a 2400 mg/m² i.v. infusion.
  • Leucovorin — OTHER
    Patients in the SoC group will receive treatment with leucovorin as part of eligible 5-FU based backbone treatment. Every 14 days during treatment phase, antibody treatment (bevacizumab 5 mg/kg or cetuximab 500 mg/m² or panitumumab 6 mg/kg) will be administered as an i.v. infusion, followed by oxaliplatin 85 mg/m² or irinotecan 180 mg/m² administered as an i.v. infusion, and leucovorin 400 mg/m2 administered as an i.v. infusion, followed by 5-FU administered as a 400 mg/m² i.v. bolus + a 2400 mg/m² i.v. infusion.

Study Details

This is a clinical research study taking place in Germany. Patients with colorectal cancer at a stage of the disease where metastases occur may take part in the study. A maximum of 90 people will participate in the study. There is already a standard therapy for treatment of colorectal cancer. This therapy contains a combination of the medicines leucovorin, fluorouracil, oxaliplatin/irinotecan and bevacizumab/cetuximab/panitumumab. The sponsoring company is developing the new therapy called arfolitixorin. In this study, patients with colorectal cancer will be given arfolitixorin instead of the standard treatment leucovorin. Different patients will receive treatment with different strengths (doses) of arfolitixorin. Treatment with fluorouracil, oxaliplatin/irinotecan and bevacizumab/cetuximab/panitumumab will also be administrated. The researchers want to find out if arfolitixorin could have an advantage over the standard therapy with leucovorin. They also want to investigate which dose of arfolitixorin is the maximum tolerated dose and if arfolitixorin is safe to use. The product being tested, arfolitixorin, like leucovorin, belongs to a group of substances called folates which are naturally occurring forms of a type of B vitamin. Folates are administered in combination with one or more chemotherapeutic agents to enhance their effect on cancer cells. The main mechanism of action of arfolitixorin is the same as that of leucovorin when used together with fluorouracil. However, leucovorin must first be converted into the active form in the body, whereas arfolitixorin already is in the active form. Leucovorin does not work equally well in all patients. By bypassing the metabolic activation of arfolitixorin, it is assumed that arfolitixorin works in a larger number of patients and has a stronger and longer efficacy in cancer treatment together with fluorouracil. However, the efficacy of arfolitixorin has not yet been proven, and the substance has not been approved for the treatment of colorectal cancer. To date, arfolitixorin has been tested by around 420 volunteers and patients with colorectal cancer in different clinical studies. These studies have shown that arfolitixorin is safe and potentially can be of clinical benefit in patients with colorectal cancer when used in combination with fluorouracil, oxaliplatin and bevacizumab. In the largest clinical study completed so far, arfolitixorin was shown to be equally effective compared to standard therapy with leucovorin, but not more effective. Additional results from this study suggested that the dose of arfolitixorin given did not deliver a sufficiently high amount of active substance into the tumor. Therefore, higher doses of arfolitixorin will be tested in this study to possibly achieve a better clinical effect. Further analyses also indicated that high accuracy regarding the timing and duration of the administration of the different treatments is important to achieve better efficacy of arfolitixorin. Based on the available data, and the risk and benefit assessments performed, the Sponsor deems that it is relevant to further investigate the safety and tolerability, as well as the efficacy of arfolitixorin when given in combination with fluorouracil, oxaliplatin/irinotecan and bevacizumab/cetuximab/panitumumab. The proposed study design is believed to address all the main previous findings with the purpose to increase the efficacy while maintaining an acceptable safety profile. The study is divided into two parts. In the first part, up to five different doses of arfolitixorin will be investigated to find the maximum tolerated dose of arfolitixorin as well as the optimal duration time of administration. The second part of the study will be based on the results from the first part. Two doses of arfolitixorin will be tested for safety, tolerability and anti-tumor effect. In the second part, participants will be randomly assigned to one of two dose groups or a control group (receiving the Standard of Care) using a computer program. This so-called randomization procedure is comparable to tossing a coin. All patients that participate in the study will receive treatment every 2 weeks. The treatment will be given as an infusion into a vein. The number of treatment administrations that will be given is not predetermined but depends on the progression of the patient's disease.The treatment will continue every 2 weeks as long as the patient benefits from the treatment. During the study period, the patient's disease and potential response to treatment, including shrinkage of the tumor and/or improvement of symptoms, will be monitored by imaging examinations, using so-called computer tomography (CT) or magnetic resonance imaging (MRI). The patient's state of health will also be monitored by physical examinations, and laboratory tests of urine and blood, as well as assessment of any side effects.

Key Dates

First listed
Apr 10, 2025
Start date
Apr 10, 2025
Status verified
Jun 2026
Primary completion
Nov 30, 2028
Completion
Dec 31, 2029

Study Design

Enrollment
90 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: High dose level
    The higher dose level of arfolitixorin in Phase 2 will be the maximum tolerated dose as determined in Phase 1b. The arfolitixorin will be given as i.v. infusion. Patients in this study will receive the IMP arfolitixorin as part of eligible 5-FU based backbone treatment (i.e., ARFOX + bevacizumab/cetuximab/panitumumab or ARFIRI + bevacizumab/cetuximab/panitumumab). The duration of the infusion will be determined in Phase 1b.
  • Experimental: Low dose level
    The lower dose level of arfolitixorin in Phase 2 will be a dose level below the maximum tolerated dose in Phase 1b, as determined by the SRC. The arfolitixorin will be given as i.v. infusion. Patients in this study will receive the IMP arfolitixorin as part of eligible 5-FU based backbone treatment (i.e., ARFOX + bevacizumab/cetuximab/panitumumab or ARFIRI + bevacizumab/cetuximab/panitumumab). The duration of the infusion will be determined in Phase 1b.
  • Active Comparator: Standard of Care (leucovorin/levoleucovorin)
    Patients in the SoC group will receive treatment with leucovorin (LV) as part of eligible 5-FU based backbone treatment (i.e., FOLFOX + bevacizumab/cetuximab/panitumumab or FOLFIRI + bevacizumab/cetuximab/panitumumab). LV will be administered as a 400 mg/m2 (for leucovorin) i.v. infusion as per the standard of care procedure at the study site and the specific label. (Note that other doses may be applicable as per the label, if e.g. levoleucovorin is given).

Primary Outcome Measure

Phase 1b: Number and severity of AEs and clinically significant abnormal laboratory findings [ Time Frame: From enrollment until end of study, i.e. until death, an average of 24 months. ]

Central Contacts

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