A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients With Early-Stage, P16-Positive, Non-Smoking Associated Oropharyngeal Cancer
Categories (click each to see list of all clinical trials associated with that category): Head & Neck (ONC), Radiation Oncology (RADONC)
Current Status: Open
Phase: II/III (Cancer Control)
Principal Investigator: Zhen, Weining
Contact Information:
Amy Filler-Katz, RN, BSN, CCRP
402-552-2790
afillerkatz@unmc.edu
Eligibility: https://clinicaltrials.gov/study/NCT03952585?term=NCT03952585&rank=1
Summary
Primary Outcome Measures :
Progression-free survival (PFS) (Phase II) [Time Frame: Up to 6 years]
Will be estimated for all Tx arms using the KM method (1958). The primary phase IIR EP will be tested using a CI approach.
PFS (Phase III) [Time Frame: Up to 6 years]
Will be estimated for all Tx arms using the KM method (1958). The co-primary phase III EP will be tested using a CI approach.
QOL [Time Frame: Baseline up to 6 years]
Measured by the MDADI global QOL score. Will be compared between arms using a two-sample independent t-test at a one-sided significance level of 0.05 for each experimental arm comparison. MDADI global score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.
Secondary Outcome Measures:
Locoregional failure [Time Frame: From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 6 years]
The cumulative incidence estimator will be used to estimate time to event distributions for locoregional failure between arm differences tested using cause-specific log-rank test.
Distant failure [Time Frame: Up to 6 years]
Overall survival [Time Frame: From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 6 years]
Will be estimated using the KM method and Tx arms compared using the log-rank test (Kaplan 1958).
Incidence of adverse events [Time Frame: Up to 6 years]
Measured by the Common Terminology Criteria for Adverse Events (CTCAE). Adverse events (AEs) will be graded using CTCAE version (v)5.0. Counts of all AEs by grade will be provided by Tx arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by Tx arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the Tx arms. A comparison between Tx arms of grade 3 and higher AEs related to Tx will also be tested. A comparison of grade 3 and higher events will be compared between Tx arms. All comparisons will be tested using a Chi-Square test, or Fisher's exact test if cell frequencies are < 5, with a significance level of 0.05.
Hearing [Time Frame: Baseline up to 24 months from end of radiation therapy (RT)]
Measured as Hearing Handicap Inventory for Adults-Screening (HHIA-S).
QOL [Time Frame: Baseline up to 24 months from end of RT]
Measured by the EORTC QLQ 30.
Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) locoregional control [Time Frame: Up to 6 years]
Will be associated with PFS.
Negative predictive value of post-RT FDG-PET/CT for locoregional control [Time Frame: At 1 and 2 years]
The negative predictive value of FDG-PET/CT for locoregional control will be estimated using binomial proportions and CI based on normal approximation.
Negative predictive value of post-RT FDG-PET/CT for PFS [Time Frame: At 1 and 2 years]
The negative predictive value of FDG-PET/CT PFS will be estimated using binomial proportions and CI based on normal approximation.
Incidence of adverse events [Time Frame: Up to 6 years]
Measured using Patient-Reported Outcomes (PRO)-CTCAE. For each symptom, counts and frequencies will be provided for the worst score experienced by the patient by Tx arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are < 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will analyzed by fitting generalized estimating equations (GEE) models using a logit link (dichotomizing the symptom scores as 0 vs. > 1 and 0-2 vs. 3-4) with time of assessment, Tx arm, and Tx-by-time interaction terms in the model.