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

NCT07419464 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202603057
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Metastatic Squamous Cell Carcinoma; Recurrent Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma of Head and Neck

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  * ORR, defined as CR and PR per RECIST v1.1. * Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Start of treatment through completion of treatment (estimated time up to 4 months)

Secondary Outcomes (10)

• Incidence of patients requiring a dose reduction due to treatment related adverse events (TRAEs)

  Start of treatment through completion of treatment (estimated time up to 4 months)

• Incidence of patients requiring a dose interruption or delay due to treatment related adverse events (TRAEs)

  Start of treatment through completion of treatment (estimated time up to 4 months)

• Incidence of patients requiring treatment discontinuation due to treatment related adverse events (TRAEs)

  Start of treatment through completion of treatment (estimated time up to 4 months)

• Daily dose intensity

  Start of treatment through completion of treatment (estimated time up to 4 months)

• Overall Adverse Events (AEs) by grade (3, 4, and 5) and type

  Start of treatment to 28 days after completion of treatment (estimated time up to 5 months)

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: 5-Fluorouracil

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

ACTIVE COMPARATOR

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.

Drug: 5-Fluorouracil

Interventions

5-Fluorouracil DRUG

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

Also known as: Adrucil, 5-FU

Arm 1: 5-Fluorouracil (5-FU) 2D-Q2W; Arm 2: 5-Fluorouracil (5-FU) 4D-Q3W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Joseph Sanchez Foundation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Laryngeal Diseases

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christine Auberle, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Auberle, MD

CONTACT

314-747-1459; auberlec@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 19, 2026
• Study Start: April 21, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2031
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)