Phase II Trial Evaluating Selective Minimal Residual Disease Directed Adjuvant Radiation in Human Papilloma Virus Associated Oropharynx Carcinoma
This study will look at whether monitoring HPV ctDNA levels is an effective way to detect cancer relapse risk in people with HPV-OPC. All participants will have recently had surgery to treat their disease, or they will be scheduled to have this surgery. In Arm A the researchers will see whether monitoring participants' HPV ctDNA levels can safely identify patients who do not need radiation therapy (RT) after surgery and whose RT can be delayed until their HPV ctDNA levels become detectable. In Arm B, the researchers will see whether patients who usually need 6-6.5 weeks of CRT can be selected by HPV ctDNA to receive 3 weeks of CRT.
• Age ≥ 18
• ECOG 0-2
• HPV-16 squamous cell carcinoma of the oropharynx or HPV-16 head and neck squamous cell carcinoma of unknown primary . HPV status must be confirmed by in-situ hybridization.
• HPV ctDNA detectable by HPV digital PCR (Naveris assay) with a minimum of 50 copies/mL pre-operatively.
• Surgical resection of all gross disease with no gross disease visualized on post-operative imaging.
• o For patients with pT0 (unknown primary) evaluation for the primary should include PET/CT, direct laryngoscopy, ipsilateral tonsillectomy, and targeted biopsy. This should be followed by a neck dissection.
• Two, undetectable (\<1 copy/mL) post-operative HPV ctDNA within 2-6 weeks following surgery (blood drawn at least one week apart preferred).
• A minimum of one of the following pathologic criteria: (Arm A)
‣ AJCC 7 Stage: pT0N1-N2b, pT1N1, pT2N1, or ≥pT3
⁃ AJCC 7 ≥pN2
⁃ Lymphovascular invasion
⁃ Perineural invasion
⁃ Close pathologic margin (≤ 3 mm)
• Signed informed consent form by the participant or their legally authorized representative (LAR).
• A minimum of one of the following pathologic criteria (Arm B):
‣ Microscopic positive margin
⁃ Extracapsular extension
• Signed informed consent form by the participant or their legally authorized representative (LAR).
∙ Additional criteria for Arm B only:
• Adequate hematologic function within 30 days prior to registration, defined as follows:
‣ White Blood Count (WBC) ≥ 2 K/mcL
⁃ Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
⁃ Platelets ≥ 100,000 cells/mm3
⁃ Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
• Adequate renal function within 30 days prior to registration, defined as follows:
‣ Serum creatinine \< 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:
⁃ CCr male = \[(140 - age) x (wt in kg)\] divided by \[(Serum Cr mg/dl) x (72)\]
⁃ CCr female = 0.85 x (CrCl male)
• Adequate hepatic function within 30 days prior to registration, defined as follows:
• \- Bilirubin \< 2 mg/dl o AST or ALT \< 3 x the upper limit of normal
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential