Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer

May 23, 2022 updated by: Radiation Therapy Oncology Group

A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

289

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • BCCA-Cancer Centre for the Southern Interior
      • Victoria, British Columbia, Canada, V8R 6V5
        • BCCA-Vancouver Island Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre at Hamilton Health Sciences
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
  • Hong Kong
      • Chai Wan, Hong Kong
        • Pamela Youde Nethersole Eastern Hospital
  • Singapore
      • Singapore, Singapore, 119074
        • National University Hospital
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
      • Phoenix, Arizona, United States, 85027
        • Arizona Oncology-Deer Valley Center
      • Scottsdale, Arizona, United States, 85260
        • Arizona Oncology Services Foundation
    • California
      • Fresno, California, United States, 93720
        • California Cancer Center - North Fresno
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland-Broadway
      • Orange, California, United States, 92868
        • Saint Joseph Hospital - Orange
      • Paradise, California, United States, 95969
        • Feather River Cancer Center
      • Pomona, California, United States, 91767
        • Pomona Valley Hospital Medical Center
      • Rancho Cordova, California, United States, 95670
        • Kaiser Permanente-Rancho Cordova Cancer Center
      • Rohnert Park, California, United States, 94928
        • Rohnert Park Cancer Center
      • Roseville, California, United States, 95678
        • The Permanente Medical Group-Roseville Radiation Oncology
      • Sacramento, California, United States, 95823
        • South Sacramento Cancer Center
      • Sacramento, California, United States, 95817
        • University of California at Davis Cancer Center
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente Cancer Treatment Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center - Anschutz Cancer Pavilion
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Littleton, Colorado, United States, 80120
        • Rocky Mountain Cancer Centers-Littleton
      • Longmont, Colorado, United States, 80501
        • Longmont United Hospital
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
      • Rehoboth Beach, Delaware, United States, 19971
        • Beebe Health Campus
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Hospital Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Science Center
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33136
        • Jackson Memorial Hospital-Holtz Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Health System
      • Atlanta, Georgia, United States, 30309
        • Piedmont Hospital
      • Atlanta, Georgia, United States, 30322
        • Emory University/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Cumming, Georgia, United States, 30041
        • Northside Hospital-Forsyth
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center
      • Savannah, Georgia, United States, 31405
        • Saint Joseph's-Candler Health System
    • Hawaii
      • 'Ewa Beach, Hawaii, United States, 96706
        • Leeward Radiation Oncology Center
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60657
        • Advocate Illinois Masonic Medical Center
      • Chicago, Illinois, United States, 60612-3785
        • John H Stroger Jr Hospital of Cook County
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
    • Indiana
      • Anderson, Indiana, United States, 46016
        • Saint Vincent Anderson Regional Hospital/Cancer Center
      • Dyer, Indiana, United States, 46311
        • Franciscan Saint Margaret Health-Dyer Campus
      • Fort Wayne, Indiana, United States, 46804
        • Radiation Oncology Associates PC
      • Hammond, Indiana, United States, 46320
        • Franciscan Saint Margaret Health-Hammond Campus
    • Iowa
      • Ames, Iowa, United States, 50010
        • McFarland Clinic PC-William R Bliss Cancer Center
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
      • Salisbury, Maryland, United States, 21801
        • Peninsula Regional Medical Center
      • Silver Spring, Maryland, United States, 20910
        • Holy Cross Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
      • Milford, Massachusetts, United States, 01757
        • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
      • South Weymouth, Massachusetts, United States, 02190
        • Dana-Farber/Brigham and Women's Cancer Center at South Shore
      • Springfield, Massachusetts, United States, 01107
        • D'Amour Center for Cancer Care
    • Michigan
      • Ann Arbor, Michigan, United States, 48106-0995
        • Saint Joseph Mercy Hospital
      • Detroit, Michigan, United States, 48236
        • Saint John Hospital and Medical Center
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health Saint Mary's
      • Warren, Michigan, United States, 48093
        • Saint John Macomb-Oakland Hospital
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
        • Sanford Clinic North-Bemidgi
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Saint John's Mercy Medical Center
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Montana
      • Billings, Montana, United States, 59107-7000
        • Billings Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • The Nebraska Medical Center
    • New Jersey
      • Mount Holly, New Jersey, United States, 08060
        • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
      • Pennington, New Jersey, United States, 08534
        • Capital Health Medical Center-Hopewell
      • Voorhees, New Jersey, United States, 08043
        • Virtua West Jersey Hospital Voorhees
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico
    • New York
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • New Hyde Park, New York, United States, 11040
        • North Shore-LIJ Health System/Center for Advanced Medicine
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
    • North Carolina
      • Supply, North Carolina, United States, 28462
        • South Atlantic Radiation Oncology
      • Wilmington, North Carolina, United States, 28401
        • Coastal Carolina Radiation Oncology
      • Wilmington, North Carolina, United States, 28401
        • New Hanover Regional Medical Center
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Akron City Hospital/Cooper Cancer Center
      • Barberton, Ohio, United States, 44203
        • Summa Barberton Hospital
      • Chardon, Ohio, United States, 44024
        • Geaugra Hospital
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43219
        • The Mark H Zangmeister Center
      • Medina, Ohio, United States, 44256
        • Summa Health Center at Lake Medina
      • Mentor, Ohio, United States, 44060
        • Lake University Ireland Cancer Center
      • Middleburg Heights, Ohio, United States, 44130
        • Southwest General Health Center Ireland Cancer Center
      • Orange Village, Ohio, United States, 44122
        • UHHS-Chagrin Highlands Medical Center
      • Portsmouth, Ohio, United States, 45662
        • Southern Ohio Medical Center
      • Westlake, Ohio, United States, 44145
        • UHHS-Westlake Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Paoli, Pennsylvania, United States, 19301
        • Paoli Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19103
        • Radiation Therapy Oncology Group
      • State College, Pennsylvania, United States, 16803
        • Mount Nittany Medical Center
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenwood, South Carolina, United States, 29646
        • Self Regional Healthcare
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Logan, Utah, United States, 84321
        • Logan Regional Hospital
      • Murray, Utah, United States, 84157
        • Intermountain Medical Center
      • Saint George, Utah, United States, 84770
        • Dixie Medical Center Regional Cancer Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
      • Salt Lake City, Utah, United States, 84143
        • LDS Hospital
    • Washington
      • Federal Way, Washington, United States, 98003
        • Saint Francis Hospital
      • Seattle, Washington, United States, 98101
        • Virginia Mason CCOP
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Edwards Comprehensive Cancer Center
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54311-6519
        • Aurora BayCare Medical Center
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  1. Pathologically proven diagnosis of endometrial or cervical cancer.
  2. Patients must have undergone a hysterectomy (total abdominal hysterectomy, vaginal hysterectomy or radical hysterectomy or total laparoscopic hysterectomy) for carcinoma of the cervix or endometrium within 49 days prior to registration. Performance of a bilateral salpingooophorectomy will be at the treating surgeon's discretion.

  3. Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

    • 3.1 History/physical examination within 45 days prior to registration;
    • 3.2 CT, MRI or positron emission tomography - computed tomography (PET-CT) including the abdomen and pelvis should be performed for initial radiological staging. This may be performed pre- or post-surgery within 90 days prior to registration. Imaging performed post-operatively should show no evidence of residual disease. Any evidence of malignancy identified on pre-operative imaging should have been completely resected surgically prior to protocol treatment.
    • 3.3 Chest CT or chest x-ray must be performed within 90 days prior to registration (unless a PET-CT has been performed)
  4. Zubrod Performance Status 0-2
  5. Age ≥ 18;

  6. Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:

    • 6.1 Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
    • 6.2 Platelets ≥ 100,000 cells/mm3;
    • 6.3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
  7. For patients receiving chemotherapy:

7.1 Within 14 days prior to registration, serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 50 cc/min. Both tests must be within these limits. The creatinine clearance should be calculated using the Cockcroft-Gault formula: (See Section 7.3.1) 7.2 Aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) 7.3 Bilirubin ≤ 2 x ULN 7.4 Alkaline phosphatase, Mg, blood urea nitrogen (BUN) and electrolytes must be obtained and recorded 8 Endometrial Cancer: 8.1 Patients with the following histologic features are eligible for pelvic radiation therapy without weekly cisplatin:

  • <50% myometrial invasion, grade 3 adenocarcinoma without uterine serous carcinoma (USC) or clear cell histology
  • ≥50% myometrial invasion grade 1-2 adenocarcinoma without USC or clear cell histology 8.2 Patients with the following histologic features may be treated with pelvic radiation with or without weekly cisplatin. The decision to add weekly cisplatin for these patients is at the treating physician's discretion:
  • ≥50% myometrial invasion, grade 3 including USC and clear cell carcinoma.
  • International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrial cancer of any grade including USC and clear cell carcinoma.
  • FIGO 2009 IIIC1 (pelvic lymph node positive only, para-aortic nodes negative if removed) including USC and clear cell carcinoma. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy. 9. Cervical Cancer: 9.1 Patients with the following pathology findings may be treated with pelvic radiation with or without weekly cisplatin at the treating physician's discretion. The decision to add weekly cisplatin for these patients is at the treating physician's discretion. 9.1.1 Patients with intermediate risk features including two of the following histologic findings after radical hysterectomy:
  • 1/3 or more stromal invasion
  • Lymph-vascular space invasion
  • Large clinical tumor diameter (> 4 cm) 9.1.2 Patients with cervical cancer treated with a simple hysterectomy with negative margins 9.2 Patients with any of the following criteria following radical hysterectomy are eligible for this study and must receive weekly cisplatin:
  • Positive resected pelvic nodes and para-aortic nodes negative if removed. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy.
  • Microscopic parametrial invasion with negative margins. 10. Patient must provide study specific informed consent prior to study entry. 11. Willingness and ability to complete the bowel and urinary domains of the EPIC prior to registration

Exclusion criteria:

  1. Patients with para-aortic nodal disease or who require extended field radiotherapy beyond the pelvis.
  2. Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or malignant mixed mullerian mixed tumor (MMMT or carcinosarcoma)
  3. Patients who exceed the weight/size limits of the treatment table or CT scanner.
  4. Mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions.
  5. Patients with evidence of metastatic disease outside of the pelvis.
  6. Patients with positive or close (< 3 mm) resection margins
  7. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
  8. Prior radiation therapy to the pelvis

  9. Patients with active inflammatory bowel disease. 10 Severe, active co-morbidity, defined as follows:

    • 10.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • 10.2 Transmural myocardial infarction within the last 6 months
    • 10.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • 10.4 Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
    • 10.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however,that laboratory test coagulation parameters are not required for entry into this protocol
    • 10.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.

11. Patients with prior treatment with platinum-based chemotherapy 12. Women who are breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intensity-Modulated Radiation Therapy
intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
Radiation: Standard radiation therapy
Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. Whole pelvis treated with a four-field technique (AP/PA/R lateral/L lateral) to 45 or 50.4 Gy at 1.8 Gy/fraction. The dose is prescribed to the isocenter which is defined as the intersection of the four beams and can be normalized to an isodose line between 97-100%. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.
Other Names:
  • RT
Active Comparator: Standard Radiation Therapy
Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy
Radiation: intensity-modulated radiation therapy
Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. All targets treated simultaneously. The vaginal planning target volume (PTV) (ITV with 7.0 mm margin) and nodal PTV receives 45 Gy in 25 fractions or 50.4 Gy in 28 fractions. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.
Other Names:
  • IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
Baseline and week 5 of RT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment
Time Frame: 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.
Baseline to Week 5 of RT
Urinary Toxicity, as Measured by Change in EPIC Urinary Domain
Time Frame: 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.
Baseline, week 3 and 5 of RT, and 4-6 weeks after RT
Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale
Time Frame: 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.
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
Health Utilities, as Measured by Change From Baseline in EQ-5D
Time Frame: 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.
Baseline, week 5 of RT, 4-6 weeks after RT
Local-regional Recurrence
Time Frame: 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.
From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Disease-free Survival
Time Frame: 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.
From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Overall Survival
Time Frame: 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.
From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers
Time Frame: Outcome measure will not be analyzed
Outcome measure will not be analyzed
Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability)
Time Frame: 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.
Baseline and week 5 of RT
Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence)
Time Frame: 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.
Baseline and week 5 of RT
Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity)
Time Frame: 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.
Baseline and week 5 of RT
Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment)
Time Frame: 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.
Baseline and week 5 of RT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI)
NRG Oncology

Investigators

  • Principal Investigator: Ann Klopp, MD, PhD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

May 20, 2022

Study Registration Dates

First Submitted

August 23, 2012

First Submitted That Met QC Criteria

August 23, 2012

First Posted (Estimate)

August 27, 2012

Study Record Updates

Last Update Posted (Actual)

June 15, 2022

Last Update Submitted That Met QC Criteria

May 23, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTOG-1203
  • CDR0000738944
  • NCI-2012-02001 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: NCT01672892-D1
    Information comments: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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