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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cancer

Intervention / Treatment
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* Genetic: DPYD or UGT1A1 variants


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cases<br>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<br>* any CLIA certified lab can be used for confirmatory testing after patients have been identified through Michigan Genomics Initiative (MGI)<br>|
| No Intervention: Controls<br>This arm will be compiled of all retrospective patients where genetic information was not known prior to receiving treatment. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DPYD, UGT1A1