Recruiting

Phase 2

5-FU Regimens5-Fluorouracil Response and Optimization STudy (The FROST Trial)

Sponsor:

Washington University School of Medicine

Code:

NCT07419464

Conditions

Squamous Cell Carcinoma of Head and Neck

Metastatic Squamous Cell Carcinoma

Recurrent Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

5-Fluorouracil

Study Details

Brief summary:

This randomized phase II trial will characterize the efficacy, adverse event (AE) profile, and safety of two regimens of 5-FU given as 2L+ treatment to patients with RM-HNSCC. Eligible patients for this trial will have previously received platinum and PD-1 inhibitor therapy. The experimental regimen (Arm 1) will comprise the two days every two weeks (2D-Q2W) regimen of 5-FU. The standard regimen (Arm 2) will consist of the four days every three weeks (4D-Q3W) regimen of 5-FU. The primary hypotheses is that each regimen of 5-FU will result in an ORR of 10% of greater assessed by RECIST v1.1 criteria. The study will also describe treatment-related AEs assessed by CTCAE v5.0, dose interruptions, discontinuations, and modifications in each regimen.

Conditions

Squamous Cell Carcinoma of Head and Neck

Metastatic Squamous Cell Carcinoma

Recurrent Squamous Cell Carcinoma of the Head and Neck

Study ID

NCT07419464

Start date

Apr 21, 2026

Status verified date

Apr, 2026

Completion date

Jul 31, 2031

Anticipated

Primary completion date

Jul 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histologically or cytologically confirmed:

RM-HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx, OR
p16+ (HPV-related) level 2-3 neck node and unknown primary site, OR
Second primary HNSCC in a previously radiated field not amenable to curative-intent surgery and/or re-radiation.
Measurable disease per RECIST 1.1.
Previously treated with platinum-based chemotherapy, RM disease within 6 months of definitive cisplatin + radiation therapy (DCisRT) or post-operative adjuvant cisplatin + radiation therapy (POACisRT) OR progressive disease on or after or intolerance to platinum agent given for RM disease.
Previously treated with PD-1 inhibitor, RM disease within 6 months of PD-1 inhibitor given as part of curative-intent therapy OR progressive disease on or after PD-1 inhibitor given for RM disease OR intolerance to prior PD-1 inhibitor in the curative or metastatic setting.
At least 18 years of age
ECOG performance status ≤ 2
Adequate bone marrow and organ function as defined below:

Absolute neutrophil count ≥ 1.0 K/cumm
Platelets ≥ 100 K/cumm
Hemoglobin ≥ 8.0 g/dL
Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3 x IULN)
AST(SGOT)/ALT(SGPT)/Alkaline Phosphatase (ALP) ≤ 3.0 x IULN. For subjects with documented bone metastasis, ALP ≤ 5.0 x IULN.
Serum creatinine <3 mg/dL or creatinine clearance > 30 mL/min by Cockcroft- Gault.
The effects of 5-FU on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after last dose of 5-FU
Recovery to baseline or ≤ grade 1 from AEs due to prior therapy, unless AEs are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, or ≤ grade 2 neuropathy are permitted.
Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

Prior 5-FU given to treat RM-HNSCC.
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
Currently receiving any other investigational agents.
RM or incurable second primary SCC of cutaneous, nasopharynx, paranasal/nasal/sinus origin.
DPYD deficiency (poor or intermediate metabolizer) as determined by next generation sequencing through blood or saliva (results of historical testing are accepted).
Severe hepatic impairment (Child-Pugh C) or history of hepatitis B or C.
Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-FU or other agents used in the study.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 14 days of study registration.
HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.

Study Design

Enrollment

46 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: 5-Fluorouracil (5-FU) 2D-Q2W

Patients randomized to Arm 1 will receive 5-FU as a 400mg/m2 bolus followed by 2,400 mg/m2 continuous intravenous infusion (CIVI) over a 46 hour time period every 2 weeks on Day 1-2 and Days 15-16. Each cycle is 28 days.

active comparator: Arm 2: 5-Fluorouracil (5-FU) 4D-Q3W

Patients randomized to Arm 2 will receive 5-FU as a 1000g/m2/day continuous intravenous infusion (CIVI) over 4 days every 3 weeks on Day 1-4. Each cycle is 21 days.

Interventions

5-Fluorouracil

Dose modifications or reductions are determined by patient's tolerability to the drug.

Primary outcome measure

Overall response rate (ORR) [ Time Frame: Start of treatment through completion of treatment (estimated time up to 4 months) ]

Central Contacts and Locations

Central contacts

Christine Auberle, MD

314-747-1459 auberlec@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Christine Auberle, MD

314-747-1459 auberlec@wustl.edu

Principal Investigator:

Christine Auberle, MD

More Information

Sponsor

Washington University School of Medicine

Last update posted

Apr 27, 2026

Last verified

Apr, 2026

Keywords

5-FU
HNSCC
RM-HNSCC
Oral cavity
Oropharynx
Larynx
Hypopharynx

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-04-27.