Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer
- Conditions
- Stage IVC Oropharyngeal Squamous Cell CarcinomaStage III Oropharyngeal Squamous Cell CarcinomaStage IVA Oropharyngeal Squamous Cell CarcinomaStage IVB Oropharyngeal Squamous Cell CarcinomaTongue Carcinoma
- Interventions
- Registration Number
- NCT02254278
- Lead Sponsor
- NRG Oncology
- Brief Summary
This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.
- Detailed Description
PRIMARY OBJECTIVES:
-To select the arm(s) achieving a 2-year progression-free survival rate of \>= 85% without unacceptable swallowing toxicity at 1 year.
SECONDARY OBJECTIVES:
* To determine patterns of failure (locoregional relapse versus distant) and survival -(overall and progression-free) at 6 months and 2 years.
* To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months.
* To determine late toxicity profiles at 1 and 2 years.
* To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years.
* To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control and progression free survival (PFS) at 2 years.
* To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years.
* To determine swallowing recovery per videofluoroscopy imaging at 2 years.
After completion of study treatment, patients are followed at 1 and 3 months then every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 316
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMRT 6 weeks + cisplatin IMRT 6 weeks IMRT 6 weeks with concurrent cisplatin IMRT 5 weeks IMRT 5 weeks IMRT 5 weeks IMRT 6 weeks + cisplatin Cisplatin IMRT 6 weeks with concurrent cisplatin
- Primary Outcome Measures
Name Time Method Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival) From randomization to 2 years Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Local-regional Failure From randomization to 2 years Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Distant metastasis and death due to other causes are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
Percentage of Participants With Distant Metastasis From randomization to 2 years Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
Percentage of Participants Alive from randomization to 2 years Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Percentage of Participants With Grade 3+ Adverse Events End of radiation therapy (RT) (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2), then 1 month, 6 months, 1 year, and two years after end of RT Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome) One year post-RT. Radiation therapy (RT) ends at approximately 6 weeks for Arm 1 and 5 weeks for Arm 2 The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.
Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years 3 months (scan) and two years after the end of RT (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2) NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.
Percentage of Participants Positive for Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) After Treatment (Detection Rate) Between 2 weeks to 1 month after treatment completion (approximately 6 weeks). Positive HPV DNA status is defined as 5 or more HPV DNA fragments per mL of blood plasma, assessed by tumor-tissue modified viral (TTMV) testing.
Change in Number of HPV DNA Fragments/mL (Copy Number) From Baseline to During Treatment (HPV DNA Rate Decline) Baseline and during treatment (obtained after 20 Gy of radiotherapy and before 28 Gy, approximately between day 10 and 14) Calculated as treatment value - baseline value. HPV DNA was assessed by tumor-tissue modified viral (TTMV) testing.
Correlation of Baseline Log HPV DNA Copy Number and Gross Tumor Volume (GTV) Baseline HPV DNA copy number is the number of HPV DNA fragments per mL of blood plasma, assessed by tumor-tissue modified viral (TTMV) testing. The natural logarithm of HPV DNA copy is used to determine correlation. GTV is the volume of the tumor determined by imaging used for treatment planning. The summary data of these two measures are reported separately in corresponding outcome measures. Correlation is measured by the Pearson correlation coefficient and ranges from -1 to +1, where ±1 indicates the strongest possible (negative or positive) correlation and 0 indicates no correlation. The study protocol indicates that participants are analyzed as a single group, treatment arms combined.
Natural Logarithm (ln) of Baseline HPV DNA Copy Number [for Purpose of Correlation] Baseline HPV DNA copy number is the number of HPV DNA fragments per mL of blood plasma, assessed by tumor-tissue modified viral (TTMV) testing. The natural logarithm of HPV DNA copy is used to determine correlation with gross tumor volume. Note that a natural log, by definition, has no units. The study protocol indicates that participants are analyzed as a single group, treatment arms combined. Correlation of Baseline Log HPV DNA Copy Number and Gross Tumor Volume (GTV) are reported in another outcome measure.
Gross Tumor Volume (GTV) [for Purpose of Correlation] Baseline GTV is the volume of the tumor determined by imaging used for radiation treatment planning. The study protocol indicates that participants are analyzed as a single group, treatment arms combined. Correlation of Baseline Log HPV DNA Copy Number and Gross Tumor Volume (GTV) are reported in another outcome measure.
HPV DNA Status by 2-year Local-regional Failure Status From end of treatment (approximate 6 weeks) to 2 years Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Positive HPV DNA status is defined as 5 or more HPV DNA fragments per mL of blood plasma, assessed by tumor-tissue modified viral (TTMV) testing.
HPV DNA Status by 2-year Progression-free Survival Status From end of treatment (approximate 6 weeks) to 2 years Progression-free survival (PFS) failure is defined as local, regional, or distant disease progression or death due to any cause. Positive HPV DNA status is defined as 5 or more HPV DNA fragments per mL of blood plasma, assessed by tumor-tissue modified viral (TTMV) testing.
Trial Locations
- Locations (222)
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Banner North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Olathe Health Cancer Center
🇺🇸Olathe, Kansas, United States
UofL Health Medical Center Northeast
🇺🇸Louisville, Kentucky, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
Scroll for more (212 remaining)UCHealth University of Colorado Hospital🇺🇸Aurora, Colorado, United States