A Phase 3 interventional study of Intensity-Modulated Radiation Therapy and Intensity-Modulated Radiation Therapy in Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 and Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7, sponsored by M.D. Anderson Cancer Center. Active, not recruiting at 22 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.
Sponsored by M.D. Anderson Cancer Center · Phase 3, Interventional, and Treatment
This randomized phase III trial studies the side effects and how well intensity-modulated proton beam therapy works and compares it to intensity-modulated photon therapy in treating patients with stage III-IVB oropharyngeal cancer. Radiation therapy uses high-energy x-rays, protons, and other types of radiation to kill tumor cells and shrink tumors. It is not yet known whether intensity-modulated proton beam therapy is more effective than intensity-modulated photon therapy in treating oropharyngeal cancer.
PRIMARY OBJECTIVES:
To compare the progression-free survival (PFS) between concurrent chemo-radiation strategies with IMRT and IMPT following the treatment of oropharyngeal tumors.
SECONDARY OBJECTIVES:
EXPLORATORY OBJECTIVE:
I. To assess potential differences between patients on study and patients who were considered eligible for randomized, were randomized to a treatment arm, but were denied insurance coverage for the treatment arm she/he was randomized to; or may have dropped out of the study for other reasons after being randomized. These patients will compromise Group 3: consisting of patients randomized to Protons but not treated and Group 4: consisting of patients randomized to IMRT but not treated at the designated institution. Furthermore, these patients will only be followed for recurrence and survival.(Phase III)
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo IMRT once daily (QD) five days a week for approximately 6.5 weeks.
ARM II: Patients undergo IMPT QD five days a week for approximately 6.5 weeks.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 5 years.
1,680 studies on the registry are indexed under Squamous Cell Carcinoma of Head and Neck; 539 are open to participants now.
This study's enrollment of 440 is above the median of 49 across 1,432 interventional studies indexed under Squamous Cell Carcinoma of Head and Neck.
Browse Squamous Cell Carcinoma of Head and Neck studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.
Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.
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Exclusion Criteria:
Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:
Patients undergo IMRT QD five days a week for approximately 6.5 weeks.
Radiation: Intensity-Modulated Radiation Therapy · Other: Laboratory Biomarker Analysis · Radiation: Photon Beam Radiation Therapy · Other: Quality-of-Life Assessment
Patients undergo IMPT QD five days a week for approximately 6.5 weeks.
Radiation: Intensity-Modulated Radiation Therapy · Other: Laboratory Biomarker Analysis · Radiation: Proton Beam Radiation Therapy · Other: Quality-of-Life Assessment
Undergo IMRT
Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Undergo IMPT
Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Correlative studies
Undergo IMRT
Also known as: Photon EBRT, Photon External Beam Radiotherapy, Radiation, Photon Beam
Undergo IMPT
Also known as: PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy, Proton Radiation Therapy, Radiation, Proton Beam
Ancillary studies
Also known as: Quality of Life Assessment
Cumulative incidence of late onset grade 3+ toxicity anytime (Phase II)
Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The methods described by Gooley will be used to estimate the cumulative incidence of late onset grade 3+ toxicity by 2 years for each treatment arm with death as a competing risk. The methods of Fine and Gray will be used to model the cumulative incidence of late onset grade 3+ toxicity by 2 years as a function of treatment arm and other potential prognostic factors (e.g., human papillomavirus (HPV)/p16 status, use of induction chemotherapy) considering death as a competing risk. Hazard ratios for the prognostic factors from this model with 95% confidence intervals will be estimated.
Time frame: Up to 2 years
Cumulative incidence of acute grade 3+ toxicity (Phase II)
Will be graded according to the NCI CTCAE version 4.0. The methods described by Gooley will be used to estimate the cumulative incidence of late onset grade 3+ toxicity by 2 years for each treatment arm with death as a competing risk. The methods of Fine and Gray will be used to model the cumulative incidence of late onset grade 3+ toxicity by 2 years as a function of treatment arm and other potential prognostic factors (e.g., HPV/p16 status, use of induction chemotherapy) considering death as a competing risk. Hazard ratios for the prognostic factors from this model with 95% confidence intervals will be estimated.
Time frame: Up to 2 years
Overall survival (OS) (Phase II)
Stratified by treatment arm and estimated using the product limit estimator of Kaplan and Meier. Cox proportional hazards regression will be used to model OS as a function of potential prognostic factors. Hazard ratios for the prognostic factors from this model will be estimated with 95% confidence intervals.
Time frame: Up to 5 years
Overall survival (Phase III)
Will be summarized at critical time points using the method of Kaplan-Meier. Kaplan-Meier plots will be used to visualize the time-to-event information by treatment arm, and the trial will be monitored based on results from log-rank tests used to compare treatment arms. Furthermore, Cox proportional hazards regression will be used to assess the time-to-event outcomes while adjusting for covariates of interest.
Time frame: Up to 5 years
Progression-free survival (Phase III)
Will be summarized at critical time points using the method of Kaplan-Meier. Kaplan-Meier plots will be used to visualize the time-to-event information by treatment arm, and the trial will be monitored based on results from log-rank tests used to compare treatment arms. Furthermore, Cox proportional hazards regression will be used to assess the time-to-event outcomes while adjusting for covariates of interest.
Time frame: Up to 3 years
Quality of life (QoL) (Phase II and III)
QoL assessments will be summarized using the mean score and standard deviation for each time point of interest. Mean response trajectories will be plotted over the time horizon for each QoL instrument administered to patients in order to explore differences between treatment arms along with other patient characteristics of interest. Other analyses such as area under the curve and linear mixed models will be used to make statistical comparisons between treatment arms while adjusting for covariates of interest.
Time frame: Up to 5 years
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Squamous Cell Carcinoma of Head and Neck→
M.D. Anderson Cancer Center