Cancer
Conditions
Keywords
DPYD, UGT1A1
Brief summary
This study will be evaluating patients suspected to carry DPYD or UGT1A1 variants based off of Michigan Genomics Initiative (MGI) results. Standard of care treatment will be initiated with either Fluoropyrimidine or Irinotecan therapy. Retrospective collection of treatment related AEs and SAEs, dose delays, dose reductions, and treatment discontinuations will be completed.
Detailed description
Trial was registered as interventional as patients could be enrolled prospectively or retrospectively. Based on data received 2/3/2025, all 16 enrolled cases ended up being identified retrospectively. As the study is now considered to be only retrospective, the record has been updated as not an applicable clinical trial (ACT).
Interventions
GENETICDPYD or UGT1A1 variants
any CLIA certified lab can be used for confirmatory testing after patients have been identified through Michigan Genomics Initiative (MGI)
Sponsors
University of Michigan Rogel Cancer Center
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Prospectively enrolled cases: A. Suspected to carry an actionable DPYD phenotype per MGI and initiating treatment with systemic FP OR suspected to carry an actionable UGT1A1 phenotype per MGI and initiating treatment with irinotecan for cancer B. The ability to understand and the willingness to sign a written informed consent. * Retrospective cases: A. Confirmed actionable DPYD phenotype before treatment with systemic FP OR confirmed actionable UGT1A1 phenotype before treatment with irinotecan B. Clinician initiated dose reduction of the fluoropyrimidine or irinotecan therapy based upon genotype result * Retrospective controls: A. Suspected actionable DPYD phenotype per MGI and treatment with systemic FP OR suspected actionable UGT1A1 phenotype per MGI and treatment with irinotecan
Exclusion criteria
* For prospective cases, prior treatment with systemic FP if suspected to carry an actionable DPYD phenotype * For prospective cases, prior treatment with irinotecan if suspected to carry an actionable UGT1A1 phenotype * For prospective cases, inability to understand consent or make health-related decisions * History of allogeneic bone marrow transplant prior to genotype testing * History of liver transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of grade 3 or higher AEs and SAEs | five months from treatment initiation | Compare rates of grade 3 or higher AEs and SAEs to fluoropyrimidine or irinotecan treatment between subjects with confirmed DPYD or UGT1A1 variants before chemotherapy treatment to retrospective matched controls without confirmatory PGx testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of PGx genotypes to MGI genotypes | five months from treatment initiation | clinical genotypes and MGI genotypes for participants will be considered concordant if they identify the same DPYD or UGT1A1 variant and discordant if they do not |
| Comparison of rates of dose reductions | five months from treatment initiation | A decrease in dose of standard of care treatment by \>10% of the dose administered for the prior cycle |
| Comparison of treatment cycle delays | five months from treatment initiation | Any prolongation of the initiation of the following scheduled treatment cycle due to toxicity as documented by the patient's medical team |
| Comparison of treatment discontinuation | five months from treatment initiation | Any discontinuation due to clinician-documented toxicity |
| Clinician acceptance of supportive care pharmacogenetics | 6 months post first standard of care treatment | Evaluation of the amount of new prescriptions written with identified genetic interactions |
Countries
United States
Outcome results
None listed