Evaluating a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy

Evaluating the Uptake and Impact of a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Genetic: DPYD or UGT1A1 variants

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).

• Study Type: Observational
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

patients who have been retrospectively identified as any patient who had clinical genotype testing and had a variant that was their clinician used to guide the chemotherapy treatment.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; This arm will be compiled of prospectively recruited cases for confirmatory testing based on their suspected genotype per Michigan Genomics Initiative and patients who have been retrospectively identified as any patient who had clinical genotype testing and had a variant that was their clinician used to guide the chemotherapy treatment. Prospective patients will undergo confirmatory genetic testing by a CLIA lab and those results will be provided to the patients clinical team at that time.	Genetic: DPYD or UGT1A1 variants; any CLIA certified lab can be used for confirmatory testing after patients have been identified through Michigan Genomics Initiative (MGI)
Controls; This arm will be compiled of all retrospective patients where genetic information was not known prior to receiving treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of grade 3 or higher AEs and SAEs	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	five months from treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of PGx genotypes to MGI genotypes	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	five months from treatment initiation
Comparison of rates of dose reductions	A decrease in dose of standard of care treatment by >10% of the dose administered for the prior cycle	five months from treatment initiation
Comparison of treatment cycle delays	Any prolongation of the initiation of the following scheduled treatment cycle due to toxicity as documented by the patient's medical team	five months from treatment initiation
Comparison of treatment discontinuation	Any discontinuation due to clinician-documented toxicity	five months from treatment initiation
Clinician acceptance of supportive care pharmacogenetics	Evaluation of the amount of new prescriptions written with identified genetic interactions	6 months post first standard of care treatment

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Amy Pasternak, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2023
• Primary Completion (Actual): June 17, 2024
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: October 13, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: UGT1A1; DPYD
• Other Study ID Numbers: UMCC 2022.062; HUM00213709 (Other Identifier: University of Michigan)

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