Implementing Pharmacogenetic Testing in Gastrointestinal Cancers

NCT04736472 | Completed Results FDA Device

• 2 other identifiers: UPCC 22220844763
• Study Type: interventional
• Target: 552
• Locations: 1 country
• Sites: 3

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.

Conditions

Gastrointestinal Cancer

Keywords

Gastrointestinal Neoplasms; Fluorouracil; Capecitabine; Irinotecan; Fluoropyrimidines; Topoisomerase I inhibitors; Antimetabolites, Antineoplastics; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (3)

• Feasibility: Number and Percentage of Participants Who Had Their Pharmacogenetic Tests Returned Prior to Initial Dose

  The Number and percentage of participants who had their pharmacogenetic tests returned prior to the first determined dose of chemotherapy.

  14 days

• Fidelity: Level of Agreement With Dose Recommendations

  The number and percentage of participants with 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 number and percentage of participants with pharmacogenetic tests ordered compared to the number of patients eligible for testing at participating sites during the study timeframe

  14 days

Secondary Outcomes (1)

• Severe Treatment Related Adverse Events (TRAE)

  6 months

Study Arms (1)

DPYD/UGT1A1 pharmacogenetic testing

EXPERIMENTAL

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

Interventions

Pharmacogenetic test DEVICE

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.

DPYD/UGT1A1 pharmacogenetic testing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (3)

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 35865463 DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Sony Tuteja, PI
• Organization: University of Pennsylvania

Sony.Tuteja@PennMedicine.upenn.edu

215-573-7834

Study Officials

• Sony Tuteja, PharmD, MS

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 3, 2021
• Study Start: March 26, 2021
• Primary Completion: December 19, 2023
• Study Completion: October 9, 2024
• Last Updated: June 6, 2025
• Results First Posted: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Study protocol, SAP, ICF will be made available 1 year following enrollment of the last participant. IPD will be made available 6 months after publication of study results.
• Access Criteria: Contact PI, Sony Tuteja, PharmD, sonyt@pennmedicine.upenn.edu with individual requests.

Locations

US (3)