DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
1 other identifier
interventional
100
1 country
12
Brief Summary
To prospectively evaluate the efficacy and safety of DPYD-guided dosing strategies in a real-world clinical setting, specifically by comparing the incidence of severe (Grade 3 and 4) fluoropyrimidine-related toxicities of heterozygous DPYD variant patients assigned to DPYD-guided reduced dosing versus patients with standard dosing in the control arm.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Aug 2025
Longer than P75 for phase_4
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 27, 2025
CompletedFirst Submitted
Initial submission to the registry
August 28, 2025
CompletedFirst Posted
Study publicly available on registry
September 5, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 7, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 7, 2029
November 13, 2025
November 1, 2025
1.9 years
August 28, 2025
November 11, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
incidence of severe fluoropyrimidine-related toxicities (Grade 3-5)
Number and proportion of patients experiencing Grade 3, 4, or 5 toxicities related to 5-FU or Capecitabine, as defined by CTCAE v5.0.
up to 24 months
Secondary Outcomes (1)
Patterns of Dose Modification (Reductions and Escalations)
up to 24 months
Study Arms (2)
Normal DPYD Patients (Control Arm)
ACTIVE COMPARATORShould receive 100% of the standard recommended doses as per the BEACON order plan. Dose Reduction for Toxicity: Reduce doses by 25% for unacceptable Grade 3 or any Grade 4 toxicity or clinically significant laboratory anbormaillity. If this occurs again, an additional 25% reduction (to 50% of the initial doses) should be used.
Patients with One DPYD Variant (Heterozygotes)
EXPERIMENTALWill receive 50% of the regular starting doses for the first two cycles. For example, for FOLFOX or FOLFIRI, the 5FU bolus would be 200 mg/m², and the infusion would be 46 hours at 1200 mg/m².
Interventions
Experimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
Experimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
Eligibility Criteria
You may qualify if:
- Diagnosis of cancer in either the adjuvant or metastatic setting requiring initial therapy with 5-FU or Capecitabine.
- DPYD testing performed by a CLIA-certified laboratory (i.e., Guardant 360 or Caris blood testing for genomic profiling, DPYD testing by the Mayo Clinic or other certified laboratory) with results available before starting chemotherapy.
- DPYD testing results falling into one of the following cohorts for first-line therapy with a fluoropyridine:
- Study Cohort: Patients with one DPYD variant in one gene (heterozygotes).
- Control Arm: Patients with normal or wild-type DPYD genes, for comparison, will be treated at the usual 100% dose.
- FOLFOX regimen (N=50)
- ECOG Performance Status 0-2.
- Measurable disease or non-measurable disease allowed, including adjuvant 5-FU-based regimens.
You may not qualify if:
- Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician.
- Patients with two DPYD variants (homozygous deletions or non-functional genetic variants, or double heterozygotes with two different abnormalities) should not receive 5-FU or Capecitabine and are therefore excluded from the study.
- Pregnant Women and Children
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
RWJBarnabas Health Clara Maas Medical Center
Belleville, New Jersey, 07109, United States
Trinitas Hospital and Comprehensive Cancer Center
Elizabeth, New Jersey, 07202, United States
RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton
Hamilton, New Jersey, 08690, United States
RWJBarnabas Health Jersey City Medical Center
Jersey City, New Jersey, 07302, United States
Cooperman Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Jack and Sheryl Morris Cancer Center
New Brunswick, New Jersey, 08901, United States
RWJBarnabas Health - Robert Wood Johnson University Hospita
New Brunswick, New Jersey, 08903, United States
Cancer Center Initiative
Newark, New Jersey, 07103, United States
University Hospital
Newark, New Jersey, 07103, United States
RWJBarnabas Health Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
RWJBarnabas Health - Robert Wood Johnson University Hospital Somerset
Somerville, New Jersey, 08873, United States
RWJBarnabas Health - Community Medical Center
Toms River, New Jersey, 08755, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Howard S. Hochster, MD
Study Principal Investigator
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Distinguished Professor of Medicine, Director Clinical Oncology Research
Study Record Dates
First Submitted
August 28, 2025
First Posted
September 5, 2025
Study Start
August 27, 2025
Primary Completion (Estimated)
July 7, 2027
Study Completion (Estimated)
July 7, 2029
Last Updated
November 13, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share