Actively Recruiting
The 5-Fluorouracil Response and Optimization STudy (The FROST Trial): A Randomized Phase II Trial of Two Dosage Regimens (2D-Q2W vs 4D-Q3W) of 5-Fluorouracil in Patients With Platinum and PD-1 Inhibitor Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Led by Washington University School of Medicine · Updated on 2026-04-27
46
Participants Needed
1
Research Sites
156 weeks
Total Duration
On this page
Sponsors
W
Washington University School of Medicine
Lead Sponsor
T
The Joseph Sanchez Foundation
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating two different dosing schedules of the drug 5-Fluorouracil (5-FU) as second-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC) who have already received platinum and PD-1 inhibitor therapies. This phase II trial aims to assess the effectiveness, safety, and side effects of these two regimens. The main goal is to see if either regimen achieves a tumor response rate of at least 10%, measured by standardized criteria. Participants will be randomly assigned to one of two treatment groups. Arm 1 receives 5-FU as a 400 mg/m2 bolus followed by a continuous intravenous infusion of 2,400 mg/m2 over 46 hours every two weeks, with each cycle lasting 28 days. Arm 2 receives 5-FU as a continuous intravenous infusion of 1,000 mg/m2 per day over four days every three weeks, with each cycle lasting 21 days. Dose adjustments may be made based on patient tolerance. Throughout the treatment period, which may last up to four months, participants will be monitored for tumor response, side effects, and treatment interruptions or discontinuations. Researchers will evaluate treatment-related adverse events, dose intensity, and survival outcomes over up to three years and four months following treatment completion. Safety assessments continue for 28 days after treatment ends, ensuring comprehensive monitoring of participants' health and response to therapy.
CONDITIONS
Brief Title
5-Fluorouracil Response and Optimization STudy (The FROST Trial)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC) of the oral cavity, oropharynx, larynx, hypopharynx, p16+ (HPV-related) neck node with unknown primary, or second primary HNSCC in a previously radiated field not suitable for curative surgery or re-radiation
- Measurable disease according to RECIST 1.1
- Previously treated with platinum-based chemotherapy for RM disease or within 6 months of definitive or post-operative cisplatin plus radiation therapy
- Previously treated with PD-1 inhibitor for RM disease or within 6 months of curative-intent therapy or intolerance to PD-1 inhibitor
- ECOG performance status of 0 to 2
- Adequate bone marrow and organ function including neutrophils ≥1.0 K/cumm, platelets ≥100 K/cumm, hemoglobin ≥8.0 g/dL, liver enzymes and bilirubin within specified limits, and creatinine clearance >30 mL/min
- Agreement to use adequate contraception during study and 30 days after last dose if of childbearing potential
- Recovery to baseline or grade 1 or less from prior therapy adverse events, except for certain low-grade controlled toxicities
- Ability to understand and sign informed consent
You will not qualify if you...
- Prior treatment with 5-FU for recurrent or metastatic head and neck squamous cell carcinoma
- Prior or concurrent malignancy that could interfere with assessment of the study treatment
- Currently receiving other investigational agents
- Recurrent or incurable second primary squamous cell carcinoma of cutaneous, nasopharynx, paranasal/nasal/sinus origin
- DPYD deficiency (poor or intermediate metabolizer) based on genetic testing
- Severe liver impairment (Child-Pugh class C) or history of hepatitis B or C
- Untreated brain metastases (treated brain metastases allowed if stable on imaging)
- History of allergic reactions to 5-FU or similar compounds
- Pregnant or breastfeeding women, or positive pregnancy test within 14 days before registration
- HIV infection without effective antiretroviral therapy and undetectable viral load for at least 6 months
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 4 months
Participants receive 5-Fluorouracil chemotherapy using one of two dosage regimens. Dose modifications or reductions may occur based on individual tolerability to the drug.
Visits every 2 or 3 weeks depending on assigned treatment arm
Duration - Up to 3 years and 4 months after treatment ends
Participants are monitored for safety and long-term outcomes including adverse events and survival after completion of treatment.
Periodic visits for safety and monitoring
Trial Site Locations
Total: 1 location
1
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
Research Team
C
Christine Auberle, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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