DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment

Summary

To prospectively evaluate the efficacy and safety of DPYD-guided dosing strategies in a real-world clinical setting, specifically by comparing the incidence of severe (Grade 3 and 4) fluoropyrimidine-related toxicities of heterozygous DPYD variant patients assigned to DPYD-guided reduced dosing versus patients with standard dosing in the control arm.

Eligibility

Inclusion Criteria:

* Diagnosis of cancer in either the adjuvant or metastatic setting requiring initial therapy with 5-FU or Capecitabine.
* DPYD testing performed by a CLIA-certified laboratory (i.e., Guardant 360 or Caris blood testing for genomic profiling, DPYD testing by the Mayo Clinic or other certified laboratory) with results available before starting chemotherapy.
* DPYD testing results falling into one of the following cohorts for first-line therapy with a fluoropyridine:
* Study Cohort: Patients with one DPYD variant in one gene (heterozygotes).
* Control Arm: Patients with normal or wild-type DPYD genes, for comparison, will be treated at the usual 100% dose.

  --FOLFOX regimen (N=50)
* ECOG Performance Status 0-2.
* Measurable disease or non-measurable disease allowed, including adjuvant 5-FU-based regimens.

Exclusion Criteria:

* Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician.
* Patients with two DPYD variants (homozygous deletions or non-functional genetic variants, or double heterozygotes with two different abnormalities) should not receive 5-FU or Capecitabine and are therefore excluded from the study.
* Pregnant Women and Children

Conditions6

Locations12 sites

Browse More Trials