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

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.