Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer
- Conditions
- Perioperative/Postoperative ComplicationsGastrointestinal ComplicationsCervical CancerEndometrial CancerRadiation ToxicityUrinary Tract ToxicityUrinary Complications
- Registration Number
- NCT01672892
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This randomized phase III trial is studying two different methods of radiation and their side effects and comparing how well they work in treating endometrial and cervical cancer after surgery.
- Detailed Description
OBJECTIVES:
Primary
* To determine if pelvic intensity-modulated radiation therapy (IMRT) reduces acute gastrointestinal toxicity in the 5th week (after 23-25 fractions) of pelvic radiation as measured with the expanded prostate cancer index composite (EPIC) instrument.
Secondary
* To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for Adverse Events version 4.0 \[CTCAE v. 4.0\]) is reduced with IMRT compared to conventional whole-pelvis radiation therapy (WPRT).
* To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT compared to conventional WPRT.
* To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
* To validate EPIC bowel and urinary domains in women undergoing either IMRT pelvic radiation treatment or four-field pelvic radiation treatment for endometrial or cervical cancer.
* To assess the impact of pelvic IMRT on quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) with cervix subscale.
* To determine if there is any difference in local-regional control, disease-free survival, and overall survival between patients treated with IMRT as compared to conventional WPRT.
* To perform a health-utilities analysis to measure the financial impact of pelvic IMRT via the EQ-5D instrument.
* To identify molecular predictors of radiation toxicity and novel circulating cancer biomarkers.
OUTLINE: This is a multicenter study. Patients are stratified according to type of cancer (endometrial vs cervical), chemotherapy (none vs 5 courses of weekly cisplatin at 40 mg/m²), and radiation dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up to 5-6 weeks.
* Arm II: Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for up to 5-6 weeks.
Some patients receive cisplatin IV over 1 hour on day 1. Treatment continues weekly for 5 weeks, concurrently with radiation therapy, in the absence of unacceptable toxicity or disease progression.
Tissue and blood samples may be collected for biomarker and correlative analysis.
Quality of life may be assessed by questionnaires (including the Expanded Prostate Cancer Index Composite \[EPIC\], the Functional Assessment of Cancer Therapy-General \[FACT-G, Version 4\], the EQ-5D, and the Common Toxicity Criteria Adverse Events - Patient-Reported Outcome \[PRO-CTCAE\]) instruments at baseline and periodically during and after study therapy.
After completion of study therapy, patients are followed every 6 months for the first 2 years and then annually for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 289
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Acute Gastrointestinal Toxicity, as Measured by Change in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score at 5 Weeks From the Start of Pelvic Radiation Baseline and week 5 of RT The primary endpoint is change in acute GI toxicity, as measured by the EPIC bowel domain, from baseline to 5 weeks after the first fraction of radiation is delivered. The EPIC has four domains (bowel, urinary, sexual, and hormonal) that have been validated separately, which allows use of only the domains of interest. The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). For each domain, responses form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, where higher scores correspond to better quality of life. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Change was calculated as follow-up score - baseline score so a negative change score indicates a decline in function.
- Secondary Outcome Measures
Name Time Method Urinary Toxicity, as Measured by Change in EPIC Urinary Domain Baseline, week 3 and 5 of RT, and 4-6 weeks after RT The primary endpoint is change in acute GI toxicity, as measured by the EPIC urinary domain, from baseline to 5 weeks after the first fraction of radiation is delivered. The EPIC has four domains (bowel, urinary, sexual, and hormonal) that have been validated separately, which allows use of only the domains of interest. The EPIC urinary domain consists of 12 items and has a function subscale (5 items) and bother subscale (7 items). For each domain, responses form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, where higher scores correspond to better quality of life. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Change was calculated as follow-up score - baseline score so a negative change score indicates a decline in function.
Overall Survival From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers Outcome measure will not be analyzed Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence) Baseline and week 5 of RT The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). The EPIC urinary domain consists of 12 total items and 4 subscales, functional (5 items), bother (7), incontinence (4) and irritative/obstructive (7). For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life. A domain score is the average of the transformed item scores. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Spearman's rank correlation coefficient is a nonparametric measure of rank correlation between two variables with a value between +1 and -1, where 1 is total positive rank correlation, 0 is no rank correlation, and -1 is total negative rank correlation.
Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity) Baseline and week 5 of RT The EPIC bowel domain and urinary domains consist of 14 and 12 items, respectively. For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life (QOL). A domain score is the average of the transformed item scores. At least 80% of the items in a domain must be completed in order to compute the score. The FACT-G is 27-item measure. Higher scores represent higher QOL. Each item has 5 responses options, 0=Not a lot and 4=Very much. Items are added together for the total score, ranging from 0-108. Certain items must be reversed before adding by subtracting the response from 4. The Pearson correlation coefficient is a measure of the linear correlation between two variables with a value between +1 and -1, where 1 is total positive linear correlation, 0 is no linear correlation, and -1 is total negative linear correlation.
Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT The FACT-G is a validated, 27-item measure where a higher score represents higher QOL. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for physical, social, functional, and 0-24 for emotional subscale. Certain items must be reversed before it is added by subtracting the response from 4. Subscale totals are summed to form the FACT-G total score. The FACT-Cx is 5-items, with score ranging 0-60, but is not included in total FACT-G. Each subscale requires \>= 50% of items completed and overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. Change calculated as follow-up score - baseline score so that a negative change score indicates a decline in function.
Health Utilities, as Measured by Change From Baseline in EQ-5D Baseline, week 5 of RT, 4-6 weeks after RT The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Both the 5-item index score and the VAS score are transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score.
Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment Baseline to Week 5 of RT Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (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 AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Disease-free Survival From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. Disease (progression) is defined as local recurrence, para-aortic recurrence, or distant metastasis. Local recurrence is defined as a disease in the radiation treatment field. Para-aortic recurrence is defined as new lymphadenopathy in the para-aortic distribution. Distant metastasis is defined as involvement of another organ or peritoneal disease. Disease-free survival time is defined as time from randomization to the date of progression, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
Local-regional Recurrence From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. Local recurrence is defined as a disease in the radiation treatment field. This can include a local vaginal recurrence or nodal disease within the field. Para-aortic recurrence is defined as new lymphadenopathy in the para-aortic distribution. Local-regional control time is defined as time from randomization to the date of local recurrence, last known follow-up (censored), or death (competing risk). Local-regional recurrence rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability) Baseline and week 5 of RT The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). The EPIC urinary domain consists of 12 total items and 4 subscales, functional (5 items), bother (7), incontinence (4) and irritative/obstructive (7). For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life. A domain score is the average of the transformed item scores. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Cronbach's alpha is an internal consistency estimate of reliability of psychometric test scores and is a function of the number of items in a test, the average covariance between item-pairs, and the variance of the total score. An alpha of 0.60-0.79 was to be considered acceptable reliability; higher than 0.8 was to be considered good reliability.
Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment) Baseline and week 5 of RT The EPIC bowel domain and urinary domains consist of 14 and 12 items, respectively. For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life (QOL). A domain score is the average of the transformed item scores. At least 80% of the items in a domain must be completed in order to compute the score. Difference is calculated as baseline - week 5.
A positive change score represents a decline in function.
Trial Locations
- Locations (137)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Arizona Oncology-Deer Valley Center
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Services Foundation
🇺🇸Scottsdale, Arizona, United States
California Cancer Center - North Fresno
🇺🇸Fresno, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸Oakland, California, United States
Saint Joseph Hospital - Orange
🇺🇸Orange, California, United States
Feather River Cancer Center
🇺🇸Paradise, California, United States
Pomona Valley Hospital Medical Center
🇺🇸Pomona, California, United States
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸Rancho Cordova, California, United States
Scroll for more (127 remaining)Banner MD Anderson Cancer Center🇺🇸Gilbert, Arizona, United States