PRIMARY OBJECTIVE:
I. To determine the 2-year recurrence rate for each arm.
SECONDARY OBJECTIVES:
I. To determine the mean percent weight loss during radiation therapy (RT) in each arm, starting at day 1 of RT and ending on the last day of RT.
II. To evaluate the proportion of patients in each arm who underwent percutaneous endoscopic gastrostomy (PEG) tube placement before RT, during RT, or after RT but within 6 weeks of completion of RT.
III. To determine the duration of need for an indwelling PEG tube (in patients who required one).
IV. To evaluate the proportion of patients in each arm taking narcotics before RT, during RT, or at 6 weeks after completion of RT.
V. To determine the adverse event (AE) profile from the day of surgery until the day before RT and during and after RT in each arm.
VI. To determine the mean change in serum creatinine during RT in each arm, starting at day 1 of RT and ending on the last day of RT.
VII. To determine the progression-free survival (PFS) and overall survival (OS) for each arm.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To document the measures of Quality of Life (QOL) at baseline, during treatment, and through two years after completion of treatment in each arm.
II. To document the proportion of patients with tumor tissue modified viral (TTMV) detected on NavDx Assay at baseline that become undetectable at 4 months after completion of radiation therapy, along with the HPV genotypes detected.
OUTLINE:
Patients undergo surgical tumor resection on study. Following surgery, patients determined to have high-risk disease are assigned to Arm 1, while patients with intermediate-risk disease are randomized to Arm 2A, 2B, or 2C. Patients with the highest- and lowest-risk disease after surgery do not continue study treatment.
ARM 1: Within 28 - 56 days after resection, patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) once daily (QD) Monday-Friday, with one day of twice daily (BID) treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients also receive cisplatin intravenously (IV) over 60 minutes once on one of the first 5 days of radiation therapy on study. Additionally, patients undergo laryngoscopy at baseline, as well as computed tomography (CT), fludeoxyglucose-positron emission tomography (FDG-PET)/CT and collection of blood samples throughout the study.
ARM 2A: Within 28 - 56 days after resection, patients undergo IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.
ARM 2B: Within 28 - 56 days after resection, patients undergo a lower dose of IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 21 treatment fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.
ARM 2C: Within 28 - 56 days after resection, patients undergo the lowest dose of IMRT or IMPT QD Monday-Friday, with one day of BID treatment, for a total of 15 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients also receive cisplatin IV over 60 minutes once on one of the first 5 days of radiation therapy on study. Additionally, patients undergo laryngoscopy at baseline, as well as CT, FDG-PET/CT and collection of blood samples throughout the study.
After completion of study treatment, patients are followed up at 6 weeks, and then at 4, 6, 12, 18, 24, 36, 48, and 60 months.
