DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment.
Study Objectives:
Primary Endpoint
- Dose modification and safety of patients with one DPYD genetic variant (heterozygous DPYD deficiency) when starting at reduced fluoropyrimidine doses.
Secondary Endpoints
- To characterize the continued doses used in heterozygous patients with DPYD variants and their ability to increase or necessity to decrease doses further.
- To characterize the specific grade and nature of fluoropyrimidine-related toxicity in all patient cohorts.
- To determine Time to Progression (TTP) on first fluoropyrimidine treatment for all patients.
- To compare rates of fluoropyrimidine dose reductions and dose intensity between DPYD variant patients and normal control patients.
Esophagus
Larynx
Lip, Oral Cavity and Pharynx
Other Digestive Organ
Pancreas
Rectum
Small Intestine
Stomach
- RWJBarnabas Health
- Community Medical Center
- Clara Maass Medical Center
- Cooperman Barnabas, Livingston
- Jersey City Medical Center, Jersey City
- Monmouth Medical Center
- Newark Beth Israel Medical Center
- Robert Wood Johnson University Hospital, Hamilton
- Robert Wood Johnson University Hospital, Somerset
- Trinitas Hospital and Comprehensive Cancer Center
- Rutgers University
Inclusion Criteria: - 1. Diagnosis of cancer in either the adjuvant or metastatic setting requiring initial therapy with 5-FU or Capecitabine. 2. 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. 3. 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) 4. ECOG Performance Status 0-2. 5. Measurable disease or non-measurable disease allowed, including adjuvant 5-FU-based regimens. Exclusion Criteria: - 1. Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician. 2. 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. 3. Pregnant Women and Children
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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