Dose Optimization and Efficacy Assessment of a Fluoropyrimidine Antidote

Launched by D'OR INSTITUTE FOR RESEARCH AND EDUCATION · Jun 13, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment to help patients who experience serious side effects from a common chemotherapy drug called fluoropyrimidine, which is used to treat cancers like breast, colon, and stomach cancer. Some patients have a hard time processing this drug, leading to severe symptoms such as nausea, vomiting, diarrhea, mouth sores, or low blood counts. The study is testing a new combination of medicines designed to act as an antidote, helping to reduce these severe side effects in patients who don’t have access to the current antidote, which is not available in Brazil.

People who might be eligible for this trial are adults with cancer who have developed significant side effects (grade 3 or higher) after receiving fluoropyrimidine chemotherapy, especially if they received a higher than recommended dose or infusion rate. Participants need to be able to take medicine by mouth and have certain organ functions within safe limits. The study requires hospitalization for at least 48 hours to closely monitor treatment and side effects. Pregnant or breastfeeding women and people with certain health conditions, like severe liver or kidney problems, are not eligible. If you join, you can expect careful medical supervision while receiving the study drug in a hospital setting, with the goal of safely reducing your chemotherapy-related toxicities.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Presence of at least one severe toxicity or intoxication resulting from fluoropyrimidine use, defined as: receiving an overdose of medication (total dose and/or infusion rate higher than recommended in the package insert) and/or Grade 3 or 4 serious adverse events after fluoropyrimidine exposure, according to CTCAE v5.0, which may include (but are not limited to): nausea, vomiting, diarrhea, anemia, neutropenia, febrile neutropenia, thrombocytopenia, and mucositis;
• • Lack of access to uridine triacetate (UT) in the standard of care;
• • Diagnosis of an invasive solid tumor under systemic treatment with a fluoropyrimidine (5-fluorouracil or capecitabine);
• • Organ function considered adequate by the investigator prior to the current fluoropyrimidine intoxication episode;
• • Ability to take oral medication;
• • For men and women of reproductive potential, agreement to practice abstinence or use highly effective contraceptive methods during study participation and for at least 6 months after the last dose of IP;
• • Men must agree not to donate sperm for at least 6 months after the last dose of IP;
• • Body surface area between 1.4 and 2.4 m², calculated using the Du Bois method;
• • AST/ALT within normal limits for participants without liver metastases;
• • AST/ALT up to 3x the upper limit of normal in participants with liver metastases;
• • Total and fractionated bilirubin up to 2x the upper limit of normal;
• • Agreement to abstain from alcohol consumption during the treatment period;
• • As a specific inclusion criterion for participants in Phase 1 of the study: a medical indication, according to routine care, for hospitalization of at least 48 hours for the clinical management of fluoropyrimidine-related toxicity.
• Exclusion Criteria:
• • Pregnant or breastfeeding women;
• • Known history of allergic reaction to the molecules of the copound and/or to other molecules in the same class;
• • Life expectancy of less than 30 days prior to hospital admission, based on underlying cancer and existing comorbidities;
• • Estimated creatinine clearance \<70 mL/min;
• • Liver cirrhosis;
• • Known liver or kidney disease;
• • Individuals with acquired immunodeficiency may be included only if they have no active opportunistic infections and following careful clinical assessment by the investigator, taking into account concurrent medications;
• • Family history or known deficiency of the enzyme responsible for metabolizing the molecules of the copound and/or to other molecules in the same class;
• • Uncontrolled infection;
• • Hemodynamically unstable patients;
• • Patients under orotracheal intubation;
• • Patients unable to take oral medication;
• • Prolonged QT interval;
• • CNS metastases considered uncontrolled by the investigator;
• • History of malabsorptive or inflammatory gastrointestinal disease;
• • Use within the last 30 days of lactulose, protease inhibitors, amiodarone, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, or rifapentine;
• • Use within the last 5 days of dietary supplements containing the molecules of the copound;
• • Use within the last 30 days of drugs classified as anticonvulsants;
• • Personal history of seizures;
• • Comorbidities deemed limiting by the investigator;
• • History of renal or liver transplant;
• • Presence of intestinal obstruction.