Therapeutic Oncolytic Monitoring as a Tool for Effective Exposure to 5-FU in Patients With Locally Advanced, Resectable Gastric or Gastro-oesophageal Junction Cancer Treated With Perioperative FLOT (THOMAS FU FLOT)

Traditional dosing of 5-FU is based on body surface area and DPD enzyme activity. However, BSA-based dosing is associated with wide inter-individual variations in 5-FU systemic exposure, and also 5-FU-induced toxicity. The international association for therapeutic drug monitoring and clinical toxicology (IATDMCT) state in there clinical guideline, in which all previous clinical pharmacokinetic studies of 5-FU were reviewed, that only 25% of the patients are within the therapeutic range. In the traditional treatment regimens a bolus of 400 mg/ m2 5-FU is given, followed by a dose of 2400 mg/m2 as a 46-hour infusion. The therapeutic range of 5-FU in these older regimens is defined by a target AUC of 20-30 mg*h/L. In contrast, 5-FU in FLOT regimen is given without a bolus, and in a high dose of 2600 mg/m2 as a 24-hour infusion. This means that a comparable absolute dose of 5-FU is given with FLOT and the older regimens, however, the manner and duration of administration differ. Based on this administration, it is expected that the FLOT regimen will result in an approximately two-fold higher steady state concentration (Css), as it is given in an approximately two-fold shorter period of time (t). As a result of this pharmacokinetic predictions, the exposure to 5-FU (AUC = Css x t) will be comparable between these different 5-FU regimens. Therefore, we hypothesise that the therapeutic range of 5-FU in FLOT will be comparable to the target AUC of 20-30 mg*h/L in the older regimens. Similar to the older treatment regimens, we expect that a significant part of patients will be outside this therapeutic window. To test these hypotheses, the aim of this study is to establish the population exposure of 5-FU in FLOT treatment regimen, and to determine the percentage of patients that achieves this therapeutic range.

Study Overview

• Status: Recruiting
• Conditions: TDM of 5-FU; Pharmacokinetic Observational Study
• Intervention / Treatment: Drug: Extra blood samples for determining exposure to 5-FU

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Thomas Manten, MSc.; Phone Number: +31652128256; Email: thomas.manten@catharinaziekenhuis.nl

Study Locations

• Netherlands
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Recruiting
      • Catharina hospital
      • Contact: Thomas Manten, MSc; Phone Number: +31652128256; Email: thomas.manten@catharinaziekenhuis.nl
      • Contact: Maarten Deenen, Dr; Phone Number: 040 239 8797; Email: maarten.deenen@catharinaziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with locally advanced, resectable gastric or gastro-esophageal junction cancer treated with perioperative FLOT.

Description

Inclusion Criteria:

1. Pathologically confirmed malignancy for which treatment with 5-FU is indicated in the FLOT regimen.
2. Age ≥ 18 years
3. Patient is able and willing to give written informed consent
4. WHO performance status 0-2
5. Patient fulfills the general treatment criteria for treatment with FLOT including appropriate liver and renal function and other standard applicable laboratory values
6. Patient is able and willing to undergo extra blood sampling for 5-FU analysis

Exclusion Criteria:

1. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient's safety.
2. Inability to undergo additional blood sampling.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with FLOT regimen; Exposure to 5-FU in patients treated with FLOT	Drug: Extra blood samples for determining exposure to 5-FU; Extra blood samples for determining exposure to 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population exposure to 5-FU	AUC of 5-FU in FLOT treated patients	1 year

Collaborators and Investigators

• Sponsor: Catharina Ziekenhuis Eindhoven

Study record dates

Study Major Dates

• Study Start (Anticipated): December 19, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: December 28, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: THOMAS FU FLOT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No