Aspirin and PAClitaxel in Head & Neck Squamous Cell Carcinoma

Prior treatment

• Prior paclitaxel or docetaxel given to treat R/M HNSCC. Prior taxane in the curative-intent setting and/or for the treatment of another cancer is permitted if the last dose was administered at least 1 year prior to enrollment.
• Palliative radiation therapy within 2 weeks of C1D1.
• 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.
• 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.
• Concurrent oral anticoagulation for a prior history of deep venous thrombosis/pulmonary embolism or atrial fibrillation.
• Concurrent aspirin or antiplatelet therapy (e.g. clopidogrel, ticagrelor) as secondary prevention for a prior history of atherosclerotic cardiovascular disease (ASCVD) requiring intervention. ASCVD events are defined as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or arterial revascularization, stroke, transient ischemic attack, and/or peripheral artery disease.

Other illness

• Clinically relevant major bleeding within the past 3 months (from screening).
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, aspirin, or other agents used in the study.

Other

• Recurrence, metastatic, or incurable second primary SCC of cutaneous, or nasopharynx origin.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 14 days of study registration.

• Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Eligible primary tumor sub-sites include oral cavity, oropharynx, larynx, hypopharynx, nasal cavity and paranasal sinus. Also allowed:
• P16+ (HPV-related) level 2-3 neck node and unknown primary
• Second primary HNSCC in a previously radiated field not amenable to curative-intent surgery and/or re-radiation
• PI3K alteration (defined in protocol) or PIK3CA amplification
• Measurable disease per RECIST 1.1.
• Previously treated with platinum-based chemotherapy in one of the following ways:
• R/M disease within 6 months of definitive cisplatin + radiation therapy (DCisRT) OR
• R/M disease within 6 months of post-operative adjuvant cisplatin + radiation therapy (POACisRT) OR
• Progressive disease on or after or intolerance to platinum agent given for R/M disease.
• Previously treated with PD-1 inhibitor in one of the following ways:
  • R/M 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 R/M disease OR
  • Intolerance to prior PD-1 inhibitor in the curative or metastatic setting OR
  • Not an appropriate candidate for PD-1 inhibitor therapy due to co-morbidity (i.e., autoimmune disease or organ/stem cell transplant)
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN (≤ 3 x IULN for subjects with Gilbert's disease)
  • AST(SGOT)/ALT(SGPT)/alkaline phosphatase (ALP) ≤ 3.0 x IULN (ALP ≤ 5.0 x IULN for subjects with documented bone metastasis)
  • Creatinine clearance \> 30 mL/min by Cockcroft-Gault
• The effects of paclitaxel 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 completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, she must inform her treating physician immediately.
• 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.