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Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI)

Primary Purpose

Gastrointestinal Cancer

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Pharmacogenetic test

About this trial

This is an interventional other trial for Gastrointestinal Cancer focused on measuring Gastrointestinal Neoplasms, Fluorouracil, Capecitabine, Irinotecan, Fluoropyrimidines, Topoisomerase I inhibitors, Antimetabolites, Antineoplastics, Molecular Mechanisms of Pharmacological Action

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Lancaster General Hospital
Penn Presbyterian Medical Center
University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DPYD/UGT1A1 pharmacogenetic testing

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility: proportion of pharmacogenetic tests returned prior to initial dose

The proportion of pharmacogenetic tests returned prior to the first determined dose of chemotherapy.

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.

Penetrance: proportion of pharmacogenetic tests ordered by providers

The proportion of pharmacogenetic tests ordered compared to the number of patient with eligible for testing

Secondary Outcome Measures

Grade 3 or higher toxicity

Proportion of patients experiencing grade 3 or higher chemotherapy induced toxicity

Full Information

NCT ID

NCT04736472

First Posted

January 29, 2021

Last Updated

June 29, 2023

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT04736472

Brief Title

Implementing Pharmacogenetic Testing in Gastrointestinal Cancers

Acronym

IMPACT-GI

Official Title

Implementing Pharmacogenetic Testing in Gastrointestinal Cancers

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 26, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Cancer

Keywords

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

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

316 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DPYD/UGT1A1 pharmacogenetic testing

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Pharmacogenetic test

Intervention Description

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.

Primary Outcome Measure Information:

Title

Feasibility: proportion of pharmacogenetic tests returned prior to initial dose

Description

The proportion of pharmacogenetic tests returned prior to the first determined dose of chemotherapy.

Time Frame

14 days

Title

Fidelity: level of agreement with dose recommendations

Description

The proportion of dose modifications made in agreement with the genotype-guided dosing recommendations for the first dose of chemotherapy.

Time Frame

14 days

Title

Penetrance: proportion of pharmacogenetic tests ordered by providers

Description

The proportion of pharmacogenetic tests ordered compared to the number of patient with eligible for testing

Time Frame

14 days

Secondary Outcome Measure Information:

Title

Grade 3 or higher toxicity

Description

Proportion of patients experiencing grade 3 or higher chemotherapy induced toxicity

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sony Tuteja, PharmD, MS

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lancaster General Hospital

City

Lancaster

State/Province

Pennsylvania

ZIP/Postal Code

17604

Country

United States

Facility Name

Penn Presbyterian Medical Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data will be made available upon reasonable request.

IPD Sharing 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.

IPD Sharing Access Criteria

Contact PI, Sony Tuteja, PharmD, sonyt@pennmedicine.upenn.edu with individual requests.

Citations:

PubMed Identifier

35865463

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.

Results Reference

derived

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