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

Not Applicable

Completed

• Conditions: Cancer

• Registration Number: NCT05583422
• Lead Sponsor: University of Michigan Rogel Cancer Center

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).

Study Timeline

• Study First Submitted: 2022-10-13
• Study First Submitted QC: 2022-10-13
• Study First Posted: 2022-10-17
• Study Start: 2023-08-18
• Primary Completion: 2024-06-17
• Study Completion: 2024-06-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University of Michigan Rogel Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States