Testing a new treatment for metastatic colorectal cancer

A Phase 1b/2 Study of Arfolitixorin Combined With 5-fluorouracil, Oxaliplatin, and Bevacizumab in First-line Treatment of Metastatic Colorectal Cancer

This study is testing a new treatment called arfolitixorin for people with metastatic colorectal cancer to see if it works better than the usual therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Isofol Medical AB (Industry-sponsored)
• Drugs / interventions: bevacizumab
• Locations: 1 site (Berlin)
• Trial ID: NCT06922383 on ClinicalTrials.gov

What this trial studies

This clinical research involves patients with metastatic colorectal cancer (mCRC) who will receive a new therapy called arfolitixorin instead of the standard treatment leucovorin. The study is designed in two phases: a Phase 1b dose-finding part followed by a randomized Phase 2 dose optimization part. Patients will be treated with arfolitixorin and bevacizumab every 14 days, with assessments conducted to evaluate safety and efficacy. The goal is to determine if arfolitixorin offers advantages over the current standard therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with RAS mutant, MSS/pMMR, colorectal adenocarcinoma at a metastatic stage, eligible for first-line therapy.

Not a fit: Patients who have previously received treatment with 5-FU, oxaliplatin, or bevacizumab for mCRC may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with metastatic colorectal cancer.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific treatment is being evaluated for the first time.

Eligibility criteria

Inclusion Criteria:

* Signed ICF and ability to comply with protocol requirements.
* Histologically confirmed RAS mutant, MSS/pMMR, colorectal adenocarcinoma with metastatic disease, eligible for first-line therapy with 5-FU, oxaliplatin, and bevacizumab regimen.
* Tumor specimen (formalin-fixed, paraffin-embedded \[FFPE\]) available.
* Adequate heart function as defined as:

  1. Heart rate ≤100 bpm.
  2. Blood pressure ≤140/90.
  3. QTc ≤430 ms (males) or ≤450 ms (females).
  4. Ejection fraction (EF) \>50%.
* Acceptable hematologic laboratory values defined as:

  1. Hemoglobin ≥90 g/L.
  2. Absolute neutrophil count ≥1.5 × 109/L.
  3. Platelets ≥100 × 109/L.
* Adequate organ function as defined by the following laboratory values:

  1. Total serum bilirubin ≤1.5 × upper limit of normal (ULN).
  2. ALT and AST ≤3 × ULN (≤5 × ULN in case of hepatic metastases).
  3. Creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (as measured according to Cockcroft-Gault equation).
* Age ≥18 years at the time of signing the ICF.
* Radiographically measurable disease per RECIST (version 1.1) within 28 days of treatment allocation.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy of \>12 weeks.
* Female patients must be surgically sterile, postmenopausal, or have negative results for a pregnancy test at screening, on a serum or urine sample obtained within 72 hours prior to initiation of study treatment.
* Female patients of childbearing potential must agree to use highly effective contraceptive measures while on study treatment (ARFOX + bevacizumab) and for at least 15 months (or longer if according to local labels) after study treatment discontinuation. Highly effective methods are those that achieve a failure rate of less than 1% per year when used consistently and correctly (as per the Clinical Trial Coordination Group \[CTCG\] Recommendations related to contraception and pregnancy testing in clinical trials, Version 1.2, 07 Mar 2024).
* Female patients should agree to refrain from egg cell donation while on study treatment (ARFOX + bevacizumab) and for at least 15 months after the last dose of study treatment.
* Male patients with female partners of childbearing potential must agree to use adequate contraceptive measures while on study treatment (ARFOX + bevacizumab) and for at least 12 months (or longer if according to local labels) after study treatment discontinuation.
* Male patients should agree to refrain from sperm donation while on study treatment (ARFOX + bevacizumab) and for at least 12 months after the last dose of study treatment.

Exclusion Criteria:

* Indication for any mCRC surgery or anti-cancer treatment other than study treatment, including but not limited to resection as confirmed by a MTB.
* Concomitant malignancies or previous malignancies with less than a 2-year disease free interval at the time of signing consent. Patients with adequately treated basal or squamous cell carcinoma of the skin, or adequately treated carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis. Patients with controlled, advanced prostate cancer are permitted. Ongoing adjuvant antihormonal therapy after breast or prostate cancer is permitted.
* Prior 5-FU, oxaliplatin or bevacizumab administration for mCRC. Or more than 6 cycles (3 months) of oxaliplatin exposure during adjuvant treatment.
* Known history of central nervous system (CNS) metastases or carcinomatous meningitis.
* Receipt of any investigational product within 14 days or 5 half-lives prior to study treatment initiation, whichever is shortest. Note that participation in any other clinical study is not allowed as long as the patient is on study treatment.
* Prior exposure to arfolitixorin.
* Major surgery, or significant traumatic injury within 8 weeks of study treatment initiation.
* Hypersensitivity to arfolitixorin, 5-FU, oxaliplatin or other platinum agent, or bevacizumab or to their excipients.
* Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency test with a Clinical Pharmacogenetics Implementation Consortium (CPIC) activity score \<1.
* Current evidence of any condition that makes participating in this study not in the best interest of the patient, including, but not limited to:

  1. Myocardial infarction or unstable angina within the past 6 months.
  2. New York Heart Association (NYHA) Class II or greater cardiac disease.
  3. Congestive heart failure.
  4. QT prolongation syndrome \>430 ms (females) and \>450 ms (males).
  5. Serious arrhythmias requiring medication for treatment.
  6. Active infection requiring i.v. antibiotics.
  7. Ongoing drug or alcohol abuse.
* Sensory peripheral neuropathy Grade ≥2.
* Pregnancy or lactation.
* Any medical condition, which in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities, or any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up schedule.

Where this trial is running

Berlin

• Charité - Universitaetsmedizin Berlin — Berlin, Germany (Recruiting)

Study contacts

• Principal investigator: Sebastian Stintzing, Prof. Dr. MD — Charité - Universitaetsmedizin Berlin, Berlin, 10117
• Study coordinator: Roger Tell, MD, PhD

Conditions Metastatic Colorectal Cancer; arfolitixorin