Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer
Phase III Randomized Trial of Intensity-Modulated Proton Beam Therapy (IMPT) Versus Intensity-Modulated Photon Therapy (IMRT) for the Treatment of Oropharyngeal Cancer of the Head and Neck
5 other identifiers
interventional
440
1 country
22
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2013
Longer than P75 for phase_3
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 2, 2013
CompletedFirst Posted
Study publicly available on registry
July 9, 2013
CompletedStudy Start
First participant enrolled
August 26, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2031
February 24, 2026
February 1, 2026
18.4 years
July 2, 2013
February 20, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
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.
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.
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.
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.
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.
Up to 3 years
Secondary Outcomes (1)
Quality of life (QoL) (Phase II and III)
Up to 5 years
Study Arms (2)
Arm I (IMRT)
EXPERIMENTALPatients undergo IMRT QD five days a week for approximately 6.5 weeks.
Arm II (IMPT)
EXPERIMENTALPatients undergo IMPT QD five days a week for approximately 6.5 weeks.
Interventions
Undergo IMRT
Undergo IMRT
Undergo IMPT
Ancillary studies
Eligibility Criteria
You may qualify if:
- Histologically documented squamous cell carcinoma of the oropharynx (American Joint Committee on Cancer \[AJCC\] version \[v\]7 stage III-IV A,B)
- Tumor tissue (primary or cervical metastasis) available for human papilloma virus (HPV) and/or p16 (in situ hybridization \[ISH\], immunohistochemistry \[IHC\] or genotyping testing); if you do not have enough leftover tumor tissue available, you will have a tumor biopsy for tumor marker testing
- Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1, or 2
- Negative pregnancy test for women of child bearing potential
- Concurrent chemotherapy
- Bilateral neck radiation
You may not qualify if:
- Previous radiation treatment for head and neck mucosal primary cancers within the past 5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity)
- Pregnant or breast-feeding females
- Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:
- Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device
- Myocardial infarction within 3 months of registration
- Distant metastases (stage IV C, any T, any N and M1)
- Previous surgical resection or neck dissection for oropharyngeal cancer, administered with therapeutic intent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Willis-Knighton Medical and Cancer Center
Shreveport, Louisiana, 71103, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
New York Proton Center
New York, New York, 10035, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
MD Anderson in The Woodlands
Conroe, Texas, 77384, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MD Anderson West Houston
Houston, Texas, 77079, United States
MD Anderson League City
League City, Texas, 77573, United States
MD Anderson in Sugar Land
Sugar Land, Texas, 77478, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (3)
Frank SJ, Busse PM, Lee JJ, Rosenthal DI, Hernandez M, Swanson DM, Garden AS, Gunn GB, Patel SH, Snider JW, Ma DJ, Molitoris JK, Lee NY, Parvathaneni U, McDonald MW, Kalman NS, Lin A, Mohammed N, Henson C, Hyde C, Bajaj GK, Katz SR, Dagan R, Morrison WH, Reddy JP, Fuller CD, Shah SJ, Phan J, Chronowski GM, Mayo L, Sturgis EM, Ferrarotto R, Zhu XR, Zhang X, Wang L, Hutcheson KA, El-Naggar AK, Moreno AC, Lee A, Spiotto MT, Gross ND, Lai SY, Liao JJ, Paly J, Liao Z, Foote RL; University of Texas MD Anderson Cancer Center Clinical Trial Consortium. Proton versus photon radiotherapy for patients with oropharyngeal cancer in the USA: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet. 2026 Jan 10;407(10524):174-184. doi: 10.1016/S0140-6736(25)01962-2. Epub 2025 Dec 11.
PMID: 41391462DERIVEDMoreno A, Sahli AJ, Johnson F, Sun X, Barbon C, Rinsurongkawong W, Song W, Luciani FM, Liang H, Li J, Liu W, Lee JJ, Frank SJ, Lai S, Fuller C, Hutcheson K; P01 MD Anderson Oropharynx Cancer Program. Stiefel MD Anderson OroPharynx cancer (MDA-OPC) cohort: a single-institution, prospective longitudinal outcomes study. BMJ Open. 2025 Nov 24;15(11):e106845. doi: 10.1136/bmjopen-2025-106845.
PMID: 41290309DERIVEDGunn GB, Blanchard P, Garden AS, Zhu XR, Fuller CD, Mohamed AS, Morrison WH, Phan J, Beadle BM, Skinner HD, Sturgis EM, Kies MS, Hutcheson KA, Rosenthal DI, Mohan R, Gillin MT, Frank SJ. Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):360-367. doi: 10.1016/j.ijrobp.2016.02.021. Epub 2016 Feb 12.
PMID: 27084653DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Steven J Frank
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 2, 2013
First Posted
July 9, 2013
Study Start
August 26, 2013
Primary Completion (Estimated)
December 31, 2031
Study Completion (Estimated)
December 31, 2031
Last Updated
February 24, 2026
Record last verified: 2026-02