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Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7Phase 3NCT01893307

Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer

A Phase 3 study testing Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis and Photon Beam Radiation Therapy in people with Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 and Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center at 22 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis and Photon Beam Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
440 participants
Where
22 sitesUnited States
Study dates
26 Aug 2013to 31 Dec 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • MD Anderson League City

    League City, Texas, 77573

  • Miami Cancer Institute

    Miami, Florida, 33176

  • New York Proton Center

    New York, New York, 10035

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Willis-Knighton Medical and Cancer Center

    Shreveport, Louisiana, 71103

  • MD Anderson in Sugar Land

    Sugar Land, Texas, 77478

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

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:

  1. To assess and compare overall survival between IMRT and IMPT along with estimating disease-related outcomes such as: [2-year progression-free survival, patterns of failure, 2-year overall survival, 2-year distant metastasis free survival, and second primary cancers]
  2. To assess acute and chronic/late side effects, and to compare the rates of Grade 3-5 toxicity between IMRT and IMPT following the treatment of oropharyngeal tumors.
  3. To assess Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI), MD Anderson Dysphagia Inventory (MDADI), FACT-HN, Xerostomia and Health Questionnaire (EQ-5D-3L), Work status (WPAI: SHP)
  4. To assess Physician Reported Toxicity using Common Terminology Criteria for Adverse Events (CTCAE)-4.0
  5. To evaluate and compare Quality-Adjusted-Life-Years (QALY) between IMPT and IMRT;
  6. To perform Cost-benefit economic analysis of treatment;
  7. To determine whether specific molecular profiles are associated with overall or progression-free survival;
  8. To investigate associations between changes in blood biomarkers, or HPV-specific cellular immune responses, or HPV ctDNA (measured at baseline and three months and at each follow-up visit for up to 10 years) with overall or progression-free survival;
  9. To bank peripheral blood at time of enrollment, weeks 2, 4, and 6 during treatment and at each follow up visits for up to 10 years to explore the ability of circulating markers to predict outcome;
  10. To bank head and neck tissues to explore the ability of tissue-based markers to predict outcome;
  11. To bank peripheral blood and tissues for future interrogations; Finally, all additional secondary endpoints

EXPLORATORY OBJECTIVE:

  1. 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.

Being tested
Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Photon Beam Radiation Therapy, Proton Beam Radiation Therapy, Quality-of-Life Assessment
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo IMPT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Photon Beam Radiation TherapyRadiation

    Also called Photon EBRT, Photon External Beam Radiotherapy, Radiation, Photon Beam

    Undergo IMRT

  • Proton Beam Radiation TherapyRadiation

    Also called PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy

    Undergo IMPT

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT01893307
Study groupRoleWhat they receive
Arm I (IMRT)ExperimentalPatients undergo IMRT QD five days a week for approximately 6.5 weeks.
Receives: Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Radiation: Photon Beam Radiation Therapy; Other: Quality-of-Life Assessment
Arm II (IMPT)ExperimentalPatients undergo IMPT QD five days a week for approximately 6.5 weeks.
Receives: Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 years

  2. 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.

    Measured: Up to 2 years

  3. 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.

    Measured: Up to 5 years

  4. 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.

    Measured: Up to 5 years

  5. 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.

    Measured: Up to 3 years

Secondary outcomes (1)

  1. 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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2013 (estimated)
  2. Study start26 Aug 2013
  3. Primary completion31 Dec 2031 (estimated)
  4. Study completion31 Dec 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
440 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01893307
Sponsor's protocol ID
2012-0825
Other IDs
NCI-2013-01879, 2012-0825, R03CA188162, R56DE025248, U19CA021239
Status last verified
Aug 2026
First submitted
2 Jul 2013
Last updated
21 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 41391462

  • Moreno 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.

    PubMed 41290309

  • Gunn 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.

    PubMed 27084653

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis and Photon Beam Radiation Therapy in people with Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 and Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative incidence of late onset grade 3+ toxicity anytime (Phase II) (time frame: Up to 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01893307, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.

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