The PhOCus Trial: Implementation of Pharmacogenomic Testing in Oncology Care

Doctors leading this study hope to find out if giving study participants' genetic information to cancer care providers will help personalize chemotherapy dosing decisions and decrease common chemotherapy side effects. Doctors leading the study will collect genetic information from study participants using pharmacogenomics/genotyping. Pharmacogenomics is the study of how the differences in our genes can affect our unique response to medications.

This is a randomized study, which means that participants in this study will be randomly assigned (as if "by flip of a coin") to one of two different groups: a "pharmacogenomics group" or "control group".

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Head and Neck Cancer; Gastrointestinal Cancer; Dihydropyrimidine Dehydrogenase Deficiency; UGT1A1 Gene Mutation
• Intervention / Treatment: Other: Availability of clinical decision support based on pharmacogenomic results.

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter H. O'Donnell, MD; Phone Number: 773-834-0936; Email: podonnel@medicine.bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Peter H. O'Donnell, MD; Phone Number: 773-834-0936; Email: podonnel@medicine.bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria Adult patients receiving oncology care at The University of Chicago Medical Center, and for whom treatment with a fluoropyrimidine and/or irinotecan is planned are eligible.

Individuals of all genders, races and ethnic groups are eligible for this trial. There is no bias towards race, sex, or gender in the clinical trial outlined.

Exclusion Criteria

1. Subjects who have previously been exposed to the planned chemotherapy agent at any time (fluoropyrimidine and/or irinotecan).
2. Subjects enrolled in an investigational trial which would preclude dose modifications of fluoropyrimidine and/or irinotecan chemotherapies.
3. Subjects who have undergone, or are being actively considered for, bone marrow, liver or kidney transplantation.
4. Subjects with a history of or active blood cancer (e.g., leukemia).
5. Chronic kidney disease, as defined by glomerular filtration rate (GFR) < 30/mL/min/1.73m2, due to the risk of decreased drug excretion.
6. Liver dysfunction, as defined by the following laboratory values, due to the risk of decreased drug metabolism: Total bilirubin more than 1.5 mg/dL, aspartate Aminotransferase (AST) and alanine transaminase (ALT) more than 2.5 X upper limit of normal*. (*AST and ALT more than 5 X upper limit of normal if hepatic metastases are present).
7. Subjects who have previously or are currently enrolled in another institutional pharmacogenomic genotyping study, or are known to have previously undergone pharmacogenomic genotyping for the gene(s) of interest via another commercial or other means.
8. Inability to understand and give informed consent to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Participants assigned to the control group will receive standard chemotherapy without their doctors receiving any genetic information based on the participants' pharmacogenetic results. DNA (Deoxyribonucleic acid) samples for participants in this group will be stored and tested for genotyping six months later after treatment (or earlier if the participant experiences side effects).
Experimental: Pharmacogenomics Group; Participants enrolled in the pharmacogenomics group will give a DNA (deoxyribonucleic acid) sample for immediate pharmacogenomic genotyping. Once the genotyping results are in, cancer doctors caring for each participant will have immediate access to clinical decision support based on the participant's genetic results and can make dosing decisions/changes to the participant's chemotherapy prescription.	Other: Availability of clinical decision support based on pharmacogenomic results.; Availability of clinical decision support based on pharmacogenomic results. These results are designed to provide specific dosing information based on the participant's unique genetics/genomics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Deviation Rate (Co-Primary Endpoint)	To assess the impact of prospective pharmacogenomic testing on dose intensity deviation rate of chemotherapy during the 1st treatment cycle, comparing control vs. pharmacogenomics-guided arms.	15 months
Grade 3 or Higher Toxicity (Co-Primary Endpoint)	To determine the degree to which providing oncologists with comprehensive pharmacogenomic information impacts the incidence of Grade 3 or worse toxicities in subjects receiving chemotherapy. Toxicities will be assessed by Common Terminology Criteria for Adverse Events version 5.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Chemotherapy Dose Intensity	Cumulative drug dose intensity received (function of dose and frequency of drug administration).	5 years.
Response Rate	Anti-cancer tumor response based on radiographic assessment (complete response, partial response, stable disease, progressive disease), by tumor type and disease setting.	5 years.
Progression free survival (PFS)	Progression free survival (PFS) by tumor type and disease setting.	5 years
Overall Survival	Overall survival (OS) by tumor type and disease setting.	5 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Peter H. O'Donnell, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacogenomics
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Purine-Pyrimidine Metabolism, Inborn Errors; Gastrointestinal Neoplasms; Dihydropyrimidine Dehydrogenase Deficiency
• Other Study ID Numbers: IRB20-0462

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No