The PhOCus Trial: Implementation of Pharmacogenomic Testing in Oncology Care

• ClinicalTrials.gov Identifier: NCT04541381
• Recruitment Status: Recruiting
• First Posted: September 9, 2020
• Last Update Posted: January 29, 2024
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Study Description

Brief Summary:

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".

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Cancer; Head and Neck Cancer; Dihydropyrimidine Dehydrogenase Deficiency; UGT1A1 Gene Mutation; Breast Cancer	Other: Availability of clinical decision support based on pharmacogenomic results.	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 860 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded
• Primary Purpose: Other
• Official Title: The PhOCus Trial: Implementation of Pharmacogenomic Testing in Oncology Care
• Actual Study Start Date: February 7, 2022
• Estimated Primary Completion Date: October 1, 2027
• Estimated Study Completion Date: March 31, 2028

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Dose Deviation Rate (Co-Primary Endpoint) [ Time Frame: 15 months ]
   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.
2. Grade 3 or Higher Toxicity (Co-Primary Endpoint) [ Time Frame: 5 years ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Peter H. O'Donnell, MD; 773-834-0936; podonnel@medicine.bsd.uchicago.edu

Locations

United States, Illinois

University of Chicago Medical Center; Recruiting

Chicago, Illinois, United States, 60637

Contact: Peter H. O'Donnell, MD 773-834-0936 podonnel@medicine.bsd.uchicago.edu

Sponsors and Collaborators

University of Chicago

Investigators

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

More Information

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT04541381
• Other Study ID Numbers: IRB20-0462
• First Posted: September 9, 2020
• Last Update Posted: January 29, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Chicago:

Pharmacogenomics

Additional relevant MeSH terms:

Gastrointestinal Neoplasms; Dihydropyrimidine Dehydrogenase Deficiency; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases