DPYD-guided fluoropyrimidine dose adjustment for patients with one DPYD gene variant
DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
PHASE4 · Rutgers, The State University of New Jersey · NCT07158164
This trial will test whether giving lower doses of fluoropyrimidine chemotherapy based on a patient's DPYD gene result reduces severe (Grade 3–4) side effects in people with colorectal, breast, or head and neck cancers who carry one DPYD variant.
Quick facts
| Phase | PHASE4 |
|---|---|
| Study type | Interventional |
| Enrollment | 100 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Rutgers, The State University of New Jersey (other) |
| Drugs / interventions | chemotherapy |
| Locations | 12 sites (Belleville, New Jersey and 11 other locations) |
| Trial ID | NCT07158164 on ClinicalTrials.gov |
What this trial studies
This is a prospective, phase 4, multi-center comparison of DPYD-guided dose reduction versus standard dosing for patients starting 5‑FU or capecitabine. Patients with a single (heterozygous) DPYD variant are assigned to reduced fluoropyrimidine dosing and compared with patients with wild-type DPYD receiving standard doses, with severe (Grade 3–4) FP-related toxicities as the primary outcome. The trial enrolls adults in adjuvant or metastatic settings and accepts both measurable and non-measurable disease, using real-world clinical workflows and CLIA-certified DPYD testing before treatment. Participating sites are regional cancer centers affiliated with Rutgers and RWJBarnabas Health in New Jersey.
Who should consider this trial
Good fit: Ideal candidates are adults with colorectal, breast, head and neck, or related gastrointestinal cancers who need initial therapy with 5‑FU or capecitabine, have CLIA-certified DPYD testing showing one DPYD variant (heterozygote), and have ECOG performance status 0–2.
Not a fit: Patients without DPYD variants (wild-type), those with contraindications to 5‑FU or capecitabine, or people with homozygous/complete DPD deficiency are unlikely to benefit from the specific dose-reduction strategy tested here.
Why it matters
Potential benefit: If successful, this approach could reduce severe, potentially life-threatening chemotherapy toxicities and make fluoropyrimidine treatment safer for patients with a DPYD variant.
How similar studies have performed: Prior pharmacogenomic research and guideline recommendations have shown that DPYD-guided dose adjustments can reduce fluoropyrimidine toxicity, but prospective real-world comparative data remain limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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. Exclusion Criteria: * 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
Where this trial is running
Belleville, New Jersey and 11 other locations
- RWJBarnabas Health Clara Maas Medical Center — Belleville, New Jersey, United States (RECRUITING)
- Trinitas Hospital and Comprehensive Cancer Center — Elizabeth, New Jersey, United States (RECRUITING)
- RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton — Hamilton, New Jersey, United States (RECRUITING)
- RWJBarnabas Health Jersey City Medical Center — Jersey City, New Jersey, United States (RECRUITING)
- Cooperman Barnabas Medical Center — Livingston, New Jersey, United States (RECRUITING)
- Jack and Sheryl Morris Cancer Center — New Brunswick, New Jersey, United States (RECRUITING)
- RWJBarnabas Health - Robert Wood Johnson University Hospita — New Brunswick, New Jersey, United States (RECRUITING)
- Cancer Center Initiative — Newark, New Jersey, United States (RECRUITING)
- University Hospital — Newark, New Jersey, United States (RECRUITING)
- RWJBarnabas Health Newark Beth Israel Medical Center — Newark, New Jersey, United States (RECRUITING)
- RWJBarnabas Health - Robert Wood Johnson University Hospital Somerset — Somerville, New Jersey, United States (RECRUITING)
- RWJBarnabas Health - Community Medical Center — Toms River, New Jersey, United States (RECRUITING)
Study contacts
- Principal investigator: Howard S. Hochster, MD — Study Principal Investigator
- Study coordinator: Howard S Hochster, MD
- Email: howard.hochster@rutgers.edu
- Phone: 732-253-5618
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Colorectal Neoplasms, Breast Neoplasms, Head and Neck Neoplasms, Gastro-Intestinal Intraepithelial Neoplasia, colorectal cancer, breast cancer, head and neck cancer, Gastro-Intestinal cancer