Neoadjuvant Chemotherapy and PD-1 Inhibition for Head and Neck Cancer Treatment De-escalation (NeoScorch HN)
The NeoScorch HN study is a single institution multisite phase II trial including 3 cohorts of 25 patients each for patients with newly diagnosed locoregionally advanced, histologically confirmed, head and neck cancer eligible for curative-intent treatment, who will receive neo-adjuvant chemoimmunotherapy-based treatment as well as standard of care adjuvant treatment. The three cohorts include three different aspects of surgical de-escalation in head and neck cancer. The first cohort includes human papillomavirus independent (HPV-) squamous cell carcinoma of the head and neck. The second cohort includes HPV-associated head and neck cancer with radiographic evidence of extranodal extension in neck lymphadenopathy. The third cohort specifically includes malignancies of the sinonasal cavity and skull base which have a propensity for invasion of the orbit, skull base, and maxilla. Surgical treatment of all three of these cohorts has significant morbidity including swallowing, speech, and vision among others.
• Eligible subjects must have histologically confirmed, locoregionally advanced head and neck or sinonasal, nasolacrimal, or skull base tumors and meet HPV testing requirements as outlined.
• HPV-independent HNSCC (cT2-cT4, N0-N3) with potential for organ preservation using response-adapted surgery.
• HPV-associated HNSCC with radiographic extranodal extension (cT1-cT3 tonsil or lateralized base of tongue, N0-N1, up to 4 nodes with rENE).
• Sinonasal/skull base tumors, including: sinonasal carcinomas, HPV-associated sinonasal cancer, sinonasal undifferentiated carcinoma (e.g., Isocitrate dehydrogenase 2 (IDH2) mutant), or neuroendocrine sinonasal tumors (e.g., olfactory neuroblastoma) (cT2-cT4, N0-N3).
• HPV16 type only. Patients with non-HPV16 cancers are not eligible. If p16 immunohistohemistry (IHC) positivity is the only result available at enrollment, neoadjuvant therapy may start while HPV nucleic acid testing is pending. Patients found to be HPV non-16 must discontinue study participation.
• At least 8 unstained 5-µm slides must be available. If unavailable, a new biopsy is required unless waived by the PI.
• Appropriate candidates for curative-intent therapy.
• American Joint Committee on Cancer (AJCC) 7th edition: Stage III-IV, excluding N2c or bulky N2b/c (N3 equivalent) and bulky T4 (≥30cc).
• AJCC 8th edition: Stage I with N1, Stage II, or Stage III, excluding N2 disease, bulky nodal disease (N3 equivalent), or bulky T4 (≥30cc).
• Surgical arm: Candidates must be operable based on upfront imaging/exam. Patients with Grade 1 rENE may proceed to surgery; Grade 2/3 rENE are excluded.
• Measurable disease per RECIST 1.1.
• No prior systemic therapy, radiotherapy, or investigational agents for the current cancer.
• No complete surgical resection within 8 weeks of enrollment (biopsy or excision with residual disease acceptable).
• Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky ≥70%.
• Platelets ≥100,000/µL.
• Absolute Neutrophil Count (ANC) ≥1,500/µL.
• Hemoglobin ≥9 g/dL (without recent transfusion/EPO).
• Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) \<2.5 × ULN.
• Albumin ≥2.5 mg/dL.
• Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ULN if total \>1.5 × ULN (Upper Limit of Normal).
• Creatinine clearance ≥60 mL/min (Cockcroft-Gault or measured GFR).
• International Normalized Ratio (INR)/ Prothrombin Time (PT) ≤1.5 × ULN (unless on anticoagulants; must be within therapeutic range).
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN (unless on anticoagulants; must be within therapeutic range).
• Must sign and understand a study-specific informed consent form.
• Women of childbearing potential (WOCBP): Negative pregnancy test within 72 hours prior to first dose.
• WOCBP must not be breastfeeding and must agree to use highly effective contraception during therapy and for 120 days after last dose.
• Men: Must use adequate contraception during treatment and for 120 days after last dose; condom use required in addition to highly effective methods.
• Azoospermic men and WOCBP not heterosexually active are exempt from contraception but must still undergo pregnancy testing.
• Counseling on pregnancy prevention is mandatory.
• Highly effective methods (\<1% failure rate with consistent use) must be used