Clinical trial NCT04736472: Implementing Pharmacogenetic Testing in Gastrointestinal Cancers
Official title: Implementing Pharmacogenetic Testing in Gastrointestinal Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastrointestinal Cancer
Keywords: Gastrointestinal Neoplasms
Fluorouracil
Capecitabine
Irinotecan
Fluoropyrimidines
Topoisomerase I inhibitors
Antimetabolites, Antineoplastics
Molecular Mechanisms of Pharmacological Action
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

1. Able and willing to provide informed consent
2. Male or female, aged 18 years or older at the time of study initiation
3. Pathologically confirmed gastrointestinal malignancy for which treatment with a fluoropyrimidine and/or irinotecan is indicated
4. Willing to undergo blood or saliva sampling for PGx testing and comply with all study-related procedures
5. Life expectancy of at least 6 months

Exclusion Criteria:

1. Prior treatment with irinotecan
2. DPYD or UGT1A1 genotype already known
3. 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)
4. Women who are pregnant or breast feeding, or subjects who refuse to use reliable contraceptive methods throughout the study
5. Treating physician does not want subject to participate

Primary outcomes:
measure: Feasibility: Number and Percentage of Participants Who Had Their Pharmacogenetic Tests Returned Prior to Initial Dose
timeFrame: 14 days
measure: Fidelity: Level of Agreement With Dose Recommendations
timeFrame: 14 days
measure: Penetrance: Proportion of Pharmacogenetic Tests Ordered by Providers
timeFrame: 14 days
Secondary outcomes:
measure: Severe Treatment Related Adverse Events (TRAE)
timeFrame: 6 months
Other outcomes:
Locations:
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Sony Tuteja, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Varughese LA, Bhupathiraju M, Hoffecker G, Terek S, Harr M, Hakonarson H, Cambareri C, Marini J, Landgraf J, Chen J, Kanter G, Lau-Min KS, Massa RC, Damjanov N, Reddy NJ, Oyer RA, Teitelbaum UR, Tuteja S. Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI): Study Protocol for a Pragmatic Implementation Trial for Establishing DPYD and UGT1A1 Screening to Guide Chemotherapy Dosing. Front Oncol. 2022 Jul 5;12:859846. doi: 10.3389/fonc.2022.859846. eCollection 2022.