Clinical trial NCT05620524: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: TDM of 5-FU
Pharmacokinetic Observational Study
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
First posted: 2022-11-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with locally advanced, resectable gastric or gastro-esophageal junction cancer treated with perioperative FLOT.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Population exposure to 5-FU
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina hospital
state: Noord-Brabant
Study officials:
References: