Squamous Cell Carcinoma of Head and NeckPhase 2NCT07419464
5-Fluorouracil Response and Optimization STudy (The FROST Trial)
A Phase 2 study testing 5-Fluorouracil in people with Squamous Cell Carcinoma of Head and Neck and Metastatic Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck, Metastatic Squamous Cell Carcinoma, Recurrent Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- 5-Fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2026to 31 Jul 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Christine Auberle, MD, 314-747-1459, auberlec@wustl.edu
Christine Auberle, MD
About this study
Official title: 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 (5-FU) in Patients With Platinum and PD-1 Inhibitor Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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
- Being tested
- 5-Fluorouracil
- Keywords
- 5-FU, HNSCC, RM-HNSCC, Oral cavity, Oropharynx, Larynx, Hypopharynx
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell, Laryngeal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
Also called Adrucil, 5-FU
Dose modifications or reductions are determined by patient's tolerability to the drug.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Start of treatment through completion of treatment (estimated time up to 4 months)
Daily dose intensity
Daily dose intensity will be measured as the average daily dose/m2 of 5-FU administered in the treatment interval for each regimen (Days 1-2 and Days 15-16 for Arm 1 and Days 1-4 for Arm 2).
Measured: 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
Adverse events are classified and graded by CTCAE v5.0.
Measured: Start of treatment to 28 days after completion of treatment (estimated time up to 5 months)
Number of adverse events of specific interest (AESI)
Adverse events of special interest are as follows: diarrhea, mucositis, palmar-plantar erythrodysesthesia (Hand-Foot Syndrome) (PPE/HRS), neutropenia, and thrombocytopenia. Adverse events are classified by CTCAE v5.0.
Measured: Start of treatment through 28 days after completion of treatment (estimated time up to 5 months)
Number of treatment-related deaths
Measured: Start of treatment through 28 days after completion of treatment (estimated time up to 5 months)
Duration of Response (DoR)
- DoR is defined as the duration from the onset of first response (CR + PR) to disease progression or death for any reason
- 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.
Measured: From time criteria is met for CR or PR through 3 years after completion of treatment (up to 3 years and 4 months)
Progression-free survival (PFS)
PFS is defined as the time from the date of treatment start to progression or death, which occurs first. The alive patients without progression are censored at the last follow-up.
Measured: Start of treatment through 3 years after completion of treatment (up to 3 years and 4 months)
Overall survival (OS)
OS is defined as the time from the start of treatment to the date of death, censored at the last follow-up otherwise.
Measured: Start of treatment through 3 years after completion of treatment (up to 3 years and 4 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2026
- Study start21 Apr 2026
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Joseph Sanchez Foundation
- Responsible party
- Sponsor
- Investigators
- Christine Auberle, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07419464
- Sponsor's protocol ID
- 202603057
- Status last verified
- Apr 2026
- First submitted
- 11 Feb 2026
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 (5-FU) in Patients With Platinum and PD-1 Inhibitor Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07419464
- Acronym / sponsor ID
- 202603057
- Conditions
- Squamous Cell Carcinoma of Head and Neck, Metastatic Squamous Cell Carcinoma, Recurrent Squamous Cell Carcinoma of the Head and Neck
- Keywords
- 5-FU, HNSCC, RM-HNSCC, Oral cavity, Oropharynx, Larynx, Hypopharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- The Joseph Sanchez Foundation
- Study start
- 21 Apr 2026 (actual)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Jul 2031 (estimated)
- First posted
- 19 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: 5-Fluorouracil (5-FU) 2D-Q2W | Experimental | Drug: 5-FluorouracilPatients 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. |
| Arm 2: 5-Fluorouracil (5-FU) 4D-Q3W | Active comparator | Drug: 5-FluorouracilPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically or cytologically confirmed:
- 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
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FluorouracilAlso: Adrucil, 5-FUDose modifications or reductions are determined by patient's tolerability to the drug. | Drug | Arm 1: 5-Fluorouracil (5-FU) 2D-Q2W, Arm 2: 5-Fluorouracil (5-FU) 4D-Q3W |
Primary outcome
Overall response rate (ORR)
Time frame: Start of treatment through completion of treatment (estimated time up to 4 months)
* 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.
10 secondary outcomes
Incidence of patients requiring a dose reduction due to treatment related adverse events (TRAEs)
Time frame: 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)
Time frame: 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)
Time frame: Start of treatment through completion of treatment (estimated time up to 4 months)
Daily dose intensity
Time frame: 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
Time frame: Start of treatment to 28 days after completion of treatment (estimated time up to 5 months)
Number of adverse events of specific interest (AESI)
Time frame: Start of treatment through 28 days after completion of treatment (estimated time up to 5 months)
Number of treatment-related deaths
Time frame: Start of treatment through 28 days after completion of treatment (estimated time up to 5 months)
Duration of Response (DoR)
Time frame: From time criteria is met for CR or PR through 3 years after completion of treatment (up to 3 years and 4 months)
Progression-free survival (PFS)
Time frame: Start of treatment through 3 years after completion of treatment (up to 3 years and 4 months)
Overall survival (OS)
Time frame: Start of treatment through 3 years after completion of treatment (up to 3 years and 4 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christine Auberle, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-Fluorouracil in people with Squamous Cell Carcinoma of Head and Neck and Metastatic Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christine Auberle, MD (314-747-1459, auberlec@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: Start of treatment through completion of treatment (estimated time up to 4 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026; AzTrials last refreshed its copy on 30 Oct 2026.