Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02254278|
Recruitment Status : Active, not recruiting
First Posted : October 1, 2014
Results First Posted : August 12, 2020
Last Update Posted : August 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Stage III Oropharyngeal Squamous Cell Carcinoma Stage IVA Oropharyngeal Squamous Cell Carcinoma Stage IVB Oropharyngeal Squamous Cell Carcinoma Stage IVC Oropharyngeal Squamous Cell Carcinoma Tongue Carcinoma||Drug: Cisplatin Radiation: IMRT 6 weeks Radiation: IMRT 5 weeks||Phase 2|
-To select the arm(s) achieving a 2-year progression-free survival rate of >= 85% without unacceptable swallowing toxicity at 1 year.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||316 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Trial for Patients With p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||June 10, 2019|
|Estimated Study Completion Date :||May 31, 2024|
Experimental: IMRT 6 weeks + cisplatin
IMRT 6 weeks with concurrent cisplatin
40 mg/m2 IV (intravenously) weekly for 6 weeks
Radiation: IMRT 6 weeks
Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Other Name: Intensity-Modulated Radiotherapy
Experimental: IMRT 5 weeks
IMRT 5 weeks
Radiation: IMRT 5 weeks
Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Other Name: Intensity-Modulated Radiotherapy
- Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival) [ Time Frame: 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.
- Percentage of Participants With Local-regional Failure [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
- Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Detection Rate [ Time Frame: Baseline to up to 2 weeks after the completion of treatment ]With a two-sided type error rate of 5% and based on chi-squared test for proportions, there is a greater than 99% power to detect HPV DNA detection rate of 65% and 95% between the 2 groups (n=140 in each arm). The rate of detection for each group will be summarized based on binomial distributions and a 95% confidence intervals (CI) will be provided.
- HPV DNA Rate Decline [ Time Frame: Baseline to up to 2 weeks after the completion of treatment ]With a two-sided type error rate of 5% and based on paired t test for means, there is 99% power to detect HPV DNA rate decline of 0.375 (effect size) within each arm (n=140). The HPV DNA rate for each group will be summarized using means and standard deviations.
- HPV DNA Copy Number [ Time Frame: Baseline to up to 2 weeks after the completion of treatment ]Correlation between HPV DNA copy number and the nodal metabolic volume will be calculated using Spearman's correlation coefficient and R2, and the corresponding 95% CI will be provided.
- Variance for HPV DNA [ Time Frame: Baseline to up to 2 weeks after the completion of treatment ]Univariable and multivariable cause specific analysis will be performed using the Cox proportional hazards model for rate of relapse.
- Change in Dysphagia Scores as Detected by Modified Barium Swallow Study and Rated by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) [ Time Frame: Baseline to 2 years after de-escalated RT ]
- Predictive Model for DIGEST Grade >= 3 Modified Barium Swallow (MBS) Detected Dysphagia [ Time Frame: 2 years after de-escalated RT ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02254278
|Principal Investigator:||Sue Yom||NRG Oncology|