Implementing Pharmacogenetic Testing in Gastrointestinal Cancers

Study Overview
=================
Brief Summary
-----------------
Pharmacogenomics (PGx) is the study of how genes affect a person's response to drugs. PGx testing for certain genes can help predict the risk of side effects from chemotherapy agents. Testing is not regularly performed in clinical practice due to long wait times for results and challenges with integrating test results in the electronic health record. Investigators leading this study hope to find out if providing cancer care providers with the ability to order a PGx test and electronically receive results with dosing recommendations will increase the use of these tests to guide treatment decisions and improve patient outcomes. This is a non-randomized implementation study, which means that all participants in this study will undergo genotyping for a pharmacogenetic test. The investigators will primarily measure the feasibility of using this test to guide cancer care.

Official Title
-----------------
Implementing Pharmacogenetic Testing in Gastrointestinal Cancers

Conditions
-----------------
Gastrointestinal Cancer

Intervention / Treatment
-----------------
* Device: Pharmacogenetic test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able and willing to provide informed consent Male or female, aged 18 years or older at the time of study initiation Pathologically confirmed gastrointestinal malignancy for which treatment with a fluoropyrimidine and/or irinotecan is indicated Willing to undergo blood or saliva sampling for PGx testing and comply with all study-related procedures Life expectancy of at least 6 months Exclusion Criteria: Prior treatment with irinotecan DPYD or UGT1A1 genotype already known Severe renal or hepatic impairment (or unacceptable laboratory values), including: Neutrophil count of <1.5 x 109/L, platelet count of <100 x 109/L Hepatic function as defined by serum bilirubin >1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >2.5 x ULN, or in case of liver metastases ALT and AST>5 x ULN Renal function as defined by serum creatinine >1.5 x ULN, or creatinine clearance <60 ml/min (by Cockcroft-Gault Equation) Women who are pregnant or breast feeding, or subjects who refuse to use reliable contraceptive methods throughout the study Treating physician does not want subject to participate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: This is a nonrandomized, open-label study to investigate the feasibility of establishing and integrating a pharmacogenetic test into clinical oncology care. A historical control group of patients with gastrointestinal cancers enrolled in a biobank will be used to compare toxicity outcomes of the prospectively-genotyped patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPYD/UGT1A1 pharmacogenetic testing<br>All patients will be screened for twelve single nucleotide polymorphisms (SNPs) in DPYD: DPYD*2A, *5, *6, *8, *9A, *10, *12, *13, rs2297595, rs115232898, rs67376798, HapB3. All patients will be screened for two SNPs in UGT1A1: UGT1A1*6, *28. | Device: Pharmacogenetic test<br>* Patients with reduced function alleles (DPYD intermediate or poor metabolizer and/or UGT1A1 poor metabolizer) will be recommended to receive dose reductions per clinical pharmacogenetic guidelines. Patients that do not carry actionable alleles (DPYD normal metabolizer and/or UGT1A1 normal or intermediate metabolizer) will receive standard dosing.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: proportion of pharmacogenetic tests returned prior to initial dose | The proportion of pharmacogenetic tests returned prior to the first determined dose of chemotherapy. | 14 days | 
| Fidelity: level of agreement with dose recommendations | The proportion of dose modifications made in agreement with the genotype-guided dosing recommendations for the first dose of chemotherapy. | 14 days | 
| Penetrance: proportion of pharmacogenetic tests ordered by providers | The proportion of pharmacogenetic tests ordered compared to the number of patient with eligible for testing | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or higher toxicity | Proportion of patients experiencing grade 3 or higher chemotherapy induced toxicity | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastrointestinal Neoplasms, Fluorouracil, Capecitabine, Irinotecan, Fluoropyrimidines, Topoisomerase I inhibitors, Antimetabolites, Antineoplastics, Molecular Mechanisms of Pharmacological Action