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.
• 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.