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

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05583422
• Collaborator: (none)
• Enrollment: 96
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 24
• Patients Per Site Per Month: 4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Genetic: DPYD or UGT1A1 variants	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Anticipated Study Start Date: Feb 1, 2023
• Anticipated Primary Completion Date: Feb 1, 2025
• Anticipated Study Completion Date: Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)
No Intervention: Controls This arm will be compiled of all retrospective patients where genetic information was not known prior to receiving treatment.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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

4. Comparison of treatment discontinuation [five months from treatment initiation]

   Any discontinuation due to clinician-documented toxicity

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age > 18 years

• Prospectively enrolled cases:

1. 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

2. The ability to understand and the willingness to sign a written informed consent.

• Retrospective cases:

1. Confirmed actionable DPYD phenotype before treatment with systemic FP OR confirmed actionable UGT1A1 phenotype before treatment with irinotecan

2. Clinician initiated dose reduction of the fluoropyrimidine or irinotecan therapy based upon genotype result

• Retrospective controls:

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT05583422
• Other Study ID Numbers: UMCC 2022.062; HUM00213709
• First Posted: Oct 17, 2022
• Last Update Posted: Dec 22, 2022
• Last Verified: Dec 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by University of Michigan Rogel Cancer Center: DPYD; UGT1A1

Study Results

No Results Posted as of Dec 22, 2022