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.
Brief Title
Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer
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:
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.
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:
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7
Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7
Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01893307
Org Class
Other
Org Full Name
M.D. Anderson Cancer Center
Org Study Id
2012-0825
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Cumulative incidence of late onset grade 3+ toxicity anytime (Phase II)
Outcome Time Frame
Up to 2 years
Outcome Description
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.
Outcome Measure
Cumulative incidence of acute grade 3+ toxicity (Phase II)
Outcome Time Frame
Up to 2 years
Outcome Description
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.
Outcome Measure
Overall survival (OS) (Phase II)
Outcome Time Frame
Up to 5 years
Outcome Description
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.
Outcome Measure
Overall survival (Phase III)
Outcome Time Frame
Up to 5 years
Outcome Description
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.
Outcome Measure
Progression-free survival (Phase III)
Outcome Time Frame
Up to 3 years
Secondary Ids
Secondary Id
NCI-2013-01879
Secondary Id
2012-0825
Secondary Id
R03CA188162
Secondary Id
R56DE025248
Secondary Id
U19CA021239
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Quality of life (QoL) (Phase II and III)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Rafi Kabarriti
Investigator Email
RKABARRI@MONTEFIORE.ORG
Investigator Phone