Risk Adapted De-Intensification of Radio-Chemotherapy for Favorable Prognosis Oropharyngeal Squamous Cell Carcinoma Based on HPV Subtype and Plasma Circulating Free HPV DNA Level and Clearance Rate
This study builds on the results of several prior studies that we have been involved with to test the hypothesis that Risk-Adapted De-Intensification of Radiation Therapy and chemotherapy based on HPV subtype, plasma circulating free HPV DNA (cfHPV DNA) level, and cfHPV DNA clearance rate produces Local-Regional Control rates that are similar to what has been achieved with more aggressive therapy in patients with Favorable Prognosis Oropharyngeal Squamous Cell Carcinoma (OPSCC).
• ≥ 18 years of age (no upper age limit)
• T0-3, N0 to N2, M0 squamous cell carcinoma of the oropharynx by AJCC 8th Edition staging. If T0 the adenopathy must be predominantly in Level 2.
• Tissue diagnosis of HPV and/or p16 positivity from the primary site or an associated lymph node.
• Radiologic confirmation of the absence of lung metastasis within 12 weeks prior to treatment; at a minimum, CT of the chest is required. PET-CT is acceptable.
• ECOG Performance Status 0-2
• ≤10 pack-years of smoking or no smoking for ≥ 10 years
• Eligible for chemotherapy
• CBC/differential obtained within 12 weeks prior to treatment, with adequate bone marrow function defined as follows:
‣ 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 and hepatic function within 12 weeks prior to treatment, defined as follows:
‣ Serum creatinine \< 2.0 mg/dl
⁃ Total bilirubin \< 2 x the institutional ULN (upper limit of normal)
⁃ AST or ALT \< 3 x the institutional ULN
⁃ Note that physician attestation of patient having no known history of liver disease can take the place of bilirubin and AST/ALT labs.
⁃ Negative pregnancy test within 3 weeks prior to treatment for women of childbearing potential.
⁃ People of childbearing potential (POCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 14 months after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, people of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
⁃ POCBP includes any person who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
‣ Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
‣ For people with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
⁃ Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 14 months following the last dose of study drug.
⁃ Patients must provide study specific informed consent prior to study entry.