Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer
Study Details
Study Description
Brief Summary
This randomized phase II/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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- To compare the rates and severity of late grade 3-5 toxicity between intensity-modulated photon therapy (IMRT) and intensity-modulated proton therapy (IMPT) following the treatment of oropharyngeal tumors. (Phase II) II. To compare the rate of 3-year progression-free survival (PFS) between concurrent chemo-radiation strategies with IMRT and IMPT following the treatment of oropharyngeal tumors. (Phase III)
SECONDARY OBJECTIVES:
- Disease-related outcomes (2-year progression-free survival, patterns of failure, 2-year overall survival, 2-year [yr] distant metastasis free survival, and second primary cancers). (Phase III) II. Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI), MD Anderson Dysphagia Inventory (MDADI), Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), Xerostomia and Health Questionnaire (European Quality of Life 5-Dimension three level scale [EQ-5D-3L]), work status (Work Productivity and Activity Impairment: Specific Health Problem [WPAI: SHP]). (Phase III) III. Physician reported toxicity using Common Terminology Criteria for Adverse Events (CTCAE)-4.0. (Phase III) IV. Quality-Adjusted-Life-Years (QALY) comparison between IMPT and IMRT. (Phase III) V. Cost-benefit economic analysis of treatment. (Phase III) VI. To determine whether specific molecular profiles are associated with overall or progression-free survival. (Phase III) VII. To investigate associations between changes in serum biomarkers or human papillomavirus (HPV)-specific cellular immune responses measured at baseline and three months with overall or progression-free survival. (Phase III) VIII. To bank peripheral blood at time of enrollment, weeks 2, 4, and 6 during treatment and during follow up visits for 2 years to explore the ability of circulating markers to predict outcome. (Phase III) IX. To bank head and neck tissues to explore the ability of tissue-based markers to predict outcome. (Phase
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- To bank peripheral blood and tissues for future interrogations. (Phase III) XI. Acute side effects of radiation therapy will be assessed. (Phase III)
EXPLORATORY OBJECTIVE:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (IMRT) Patients undergo IMRT QD five days a week for approximately 6.5 weeks. |
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Photon Beam Radiation Therapy
Undergo IMRT
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
|
| Experimental: Arm II (IMPT) Patients undergo IMPT QD five days a week for approximately 6.5 weeks. |
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMPT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Proton Beam Radiation Therapy
Undergo IMPT
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cumulative incidence of late onset grade 3+ toxicity anytime (Phase II) [Up to 2 years]
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.
- Cumulative incidence of acute grade 3+ toxicity (Phase II) [Up to 2 years]
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.
- Overall survival (OS) (Phase II) [Up to 5 years]
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.
- Overall survival (Phase III) [Up to 5 years]
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.
- Progression-free survival (Phase III) [Up to 3 years]
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.
Secondary Outcome Measures
- Quality of life (QoL) (Phase II and III) [Up to 5 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically documented squamous cell carcinoma of the oropharynx (American Joint Committee on Cancer [AJCC] version [v]7 stage III-IV A,B)
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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
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Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1, or 2
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Negative pregnancy test for women of child bearing potential
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Concurrent chemotherapy
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Bilateral neck radiation
Exclusion Criteria:
-
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
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Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:
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Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device
-
Myocardial infarction within 3 months of registration
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Distant metastases (stage IV C, any T, any N and M1)
-
Previous surgical resection or neck dissection for oropharyngeal cancer, administered with therapeutic intent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35249 |
| 2 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259 |
| 3 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 4 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
| 5 | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 6 | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois | United States | 60555 |
| 7 | Willis-Knighton Medical and Cancer Center | Shreveport | Louisiana | United States | 71103 |
| 8 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 9 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 10 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 11 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 12 | New York Proton Center | New York | New York | United States | 10035 |
| 13 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 14 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 15 | University of Pennsylvania/Abramson Cancer Center | Philadelphia | Pennsylvania | United States | 19104 |
| 16 | MD Anderson in The Woodlands | Conroe | Texas | United States | 77384 |
| 17 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 18 | MD Anderson West Houston | Houston | Texas | United States | 77079 |
| 19 | MD Anderson League City | League City | Texas | United States | 77573 |
| 20 | MD Anderson in Sugar Land | Sugar Land | Texas | United States | 77478 |
| 21 | Inova Schar Cancer Institute | Fairfax | Virginia | United States | 22031 |
| 22 | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
- National Institute of Dental and Craniofacial Research (NIDCR)
Investigators
- Principal Investigator: Steven J Frank, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2012-0825
- NCI-2013-01879
- 2012-0825
- R03CA188162
- R56DE025248
- U19CA021239