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

Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 Clinical Trial

Official title:

Phase II/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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01893307
• Other study ID #: 2012-0825
• Secondary ID: NCI-2013-0187920
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: August 26, 2013
• Est. completion date: August 31, 2025

Study information

• Verified date: March 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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 III) X. 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:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 440
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

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

• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oropharyngeal Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7
• Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7
• Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Intervention

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT
• Intensity-Modulated Radiation Therapy
Undergo IMPT

Other:
• Laboratory Biomarker Analysis
Correlative studies

Radiation:
• Photon Beam Radiation Therapy
Undergo IMRT
• Proton Beam Radiation Therapy
Undergo IMPT

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	MD Anderson League City	League City	Texas
United States	Miami Cancer Institute	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Proton Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington
United States	Willis-Knighton Medical and Cancer Center	Shreveport	Louisiana
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI), National Institute of Dental and Craniofacial Research (NIDCR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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.	Up to 5 years

External Links

•   M D Anderson Cancer Center website