Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer
A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)
3 other identifiers
interventional
289
4 countries
137
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2012
Longer than P75 for phase_3
137 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 23, 2012
CompletedFirst Posted
Study publicly available on registry
August 27, 2012
CompletedStudy Start
First participant enrolled
November 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedResults Posted
Study results publicly available
January 23, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2022
CompletedJune 15, 2022
May 1, 2022
3.1 years
August 23, 2012
October 3, 2017
May 23, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
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 Outcomes (12)
Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment
Baseline to Week 5 of RT
Urinary Toxicity, as Measured by Change in EPIC Urinary Domain
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
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
Baseline, week 5 of RT, 4-6 weeks after RT
Local-regional Recurrence
From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
- +7 more secondary outcomes
Study Arms (2)
Intensity-Modulated Radiation Therapy
EXPERIMENTALintensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
Standard Radiation Therapy
ACTIVE COMPARATORStandard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- Pathologically proven diagnosis of endometrial or cervical cancer.
- 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.
- Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- History/physical examination within 45 days prior to registration;
- 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.
- Chest CT or chest x-ray must be performed within 90 days prior to registration (unless a PET-CT has been performed)
- Zubrod Performance Status 0-2
- Age ≥ 18;
- Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
- For patients receiving chemotherapy:
- 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
- +9 more criteria
You may not qualify if:
- Patients with para-aortic nodal disease or who require extended field radiotherapy beyond the pelvis.
- Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or malignant mixed mullerian mixed tumor (MMMT or carcinosarcoma)
- Patients who exceed the weight/size limits of the treatment table or CT scanner.
- Mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions.
- Patients with evidence of metastatic disease outside of the pelvis.
- Patients with positive or close (\< 3 mm) resection margins
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
- Prior radiation therapy to the pelvis
- Patients with active inflammatory bowel disease. 10 Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
- 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
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Radiation Therapy Oncology Grouplead
- National Cancer Institute (NCI)collaborator
- NRG Oncologycollaborator
Study Sites (137)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Arizona Oncology-Deer Valley Center
Phoenix, Arizona, 85027, United States
Arizona Oncology Services Foundation
Scottsdale, Arizona, 85260, United States
California Cancer Center - North Fresno
Fresno, California, 93720, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Kaiser Permanente Oakland-Broadway
Oakland, California, 94611, United States
Saint Joseph Hospital - Orange
Orange, California, 92868, United States
Feather River Cancer Center
Paradise, California, 95969, United States
Pomona Valley Hospital Medical Center
Pomona, California, 91767, United States
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova, California, 95670, United States
Rohnert Park Cancer Center
Rohnert Park, California, 94928, United States
The Permanente Medical Group-Roseville Radiation Oncology
Roseville, California, 95678, United States
University of California at Davis Cancer Center
Sacramento, California, 95817, United States
South Sacramento Cancer Center
Sacramento, California, 95823, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051, United States
Kaiser Permanente Cancer Treatment Center
South San Francisco, California, 94080, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907, United States
Porter Adventist Hospital
Denver, Colorado, 80210, United States
Swedish Medical Center
Englewood, Colorado, 80113, United States
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado, 80120, United States
Longmont United Hospital
Longmont, Colorado, 80501, United States
McKee Medical Center
Loveland, Colorado, 80539, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718, United States
Beebe Health Campus
Rehoboth Beach, Delaware, 19971, United States
Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
University of Florida
Gainesville, Florida, 32610, United States
University of Florida Health Science Center
Jacksonville, Florida, 32209, United States
Jackson Memorial Hospital-Holtz Children's Hospital
Miami, Florida, 33136, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Piedmont Hospital
Atlanta, Georgia, 30309, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Northside Hospital-Forsyth
Cumming, Georgia, 30041, United States
Northeast Georgia Medical Center
Gainesville, Georgia, 30501, United States
Saint Joseph's-Candler Health System
Savannah, Georgia, 31405, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
University of Hawaii
Honolulu, Hawaii, 96813, United States
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817, United States
Leeward Radiation Oncology Center
‘Ewa Beach, Hawaii, 96706, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Northwestern University
Chicago, Illinois, 60611, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612-3785, United States
University of Illinois
Chicago, Illinois, 60612, United States
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Saint Vincent Anderson Regional Hospital/Cancer Center
Anderson, Indiana, 46016, United States
Franciscan Saint Margaret Health-Dyer Campus
Dyer, Indiana, 46311, United States
Radiation Oncology Associates PC
Fort Wayne, Indiana, 46804, United States
Franciscan Saint Margaret Health-Hammond Campus
Hammond, Indiana, 46320, United States
McFarland Clinic PC-William R Bliss Cancer Center
Ames, Iowa, 50010, United States
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Greater Baltimore Medical Center
Baltimore, Maryland, 21204, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Peninsula Regional Medical Center
Salisbury, Maryland, 21801, United States
Holy Cross Hospital
Silver Spring, Maryland, 20910, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Lowell General Hospital
Lowell, Massachusetts, 01854, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
Milford, Massachusetts, 01757, United States
Dana-Farber/Brigham and Women's Cancer Center at South Shore
South Weymouth, Massachusetts, 02190, United States
D'Amour Center for Cancer Care
Springfield, Massachusetts, 01107, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Saint John Hospital and Medical Center
Detroit, Michigan, 48236, United States
Mercy Health Saint Mary's
Grand Rapids, Michigan, 49503, United States
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503, United States
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093, United States
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, 56601, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
CoxHealth South Hospital
Springfield, Missouri, 65807, United States
Saint John's Mercy Medical Center
St Louis, Missouri, 63141, United States
Billings Clinic
Billings, Montana, 59107-7000, United States
The Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
Mount Holly, New Jersey, 08060, United States
Capital Health Medical Center-Hopewell
Pennington, New Jersey, 08534, United States
Virtua West Jersey Hospital Voorhees
Voorhees Township, New Jersey, 08043, United States
University of New Mexico
Albuquerque, New Mexico, 87106, United States
Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, 11040, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
South Atlantic Radiation Oncology
Supply, North Carolina, 28462, United States
Coastal Carolina Radiation Oncology
Wilmington, North Carolina, 28401, United States
New Hanover Regional Medical Center
Wilmington, North Carolina, 28401, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, 44304, United States
Summa Barberton Hospital
Barberton, Ohio, 44203, United States
Geaugra Hospital
Chardon, Ohio, 44024, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
The Mark H Zangmeister Center
Columbus, Ohio, 43219, United States
Summa Health Center at Lake Medina
Medina, Ohio, 44256, United States
Lake University Ireland Cancer Center
Mentor, Ohio, 44060, United States
Southwest General Health Center Ireland Cancer Center
Middleburg Heights, Ohio, 44130, United States
UHHS-Chagrin Highlands Medical Center
Orange, Ohio, 44122, United States
Southern Ohio Medical Center
Portsmouth, Ohio, 45662, United States
UHHS-Westlake Medical Center
Westlake, Ohio, 44145, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Abington Memorial Hospital
Abington, Pennsylvania, 19001, United States
Paoli Memorial Hospital
Paoli, Pennsylvania, 19301, United States
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, 19103, United States
Mount Nittany Medical Center
State College, Pennsylvania, 16803, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Lankenau Hospital
Wynnewood, Pennsylvania, 19096, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Self Regional Healthcare
Greenwood, South Carolina, 29646, United States
Rapid City Regional Hospital
Rapid City, South Dakota, 57701, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Logan Regional Hospital
Logan, Utah, 84321, United States
Intermountain Medical Center
Murray, Utah, 84157, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
Dixie Medical Center Regional Cancer Center
St. George, Utah, 84770, United States
Saint Francis Hospital
Federal Way, Washington, 98003, United States
Virginia Mason CCOP
Seattle, Washington, 98101, United States
Edwards Comprehensive Cancer Center
Huntington, West Virginia, 25701, United States
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311-6519, United States
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Aurora West Allis Medical Center
West Allis, Wisconsin, 53227, United States
BCCA-Cancer Centre for the Southern Interior
Kelowna, British Columbia, V1Y 5L3, Canada
BCCA-Vancouver Island Cancer Centre
Victoria, British Columbia, V8R 6V5, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2, Canada
London Regional Cancer Program
London, Ontario, N6A 4L6, Canada
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1, Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4, Canada
Pamela Youde Nethersole Eastern Hospital
Chai Wan, Hong Kong
National University Hospital
Singapore, 119074, Singapore
Related Publications (4)
Yeung AR, Pugh SL, Klopp AH, Gil KM, Wenzel L, Westin SN, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Deshmukh S, Bruner DW, Kachnic LA. Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study. J Clin Oncol. 2020 May 20;38(15):1685-1692. doi: 10.1200/JCO.19.02381. Epub 2020 Feb 19.
PMID: 32073955BACKGROUNDGil KM, Pugh SL, Klopp AH, Yeung AR, Wenzel L, Westin SN, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Deshmukh S, Kachnic LA, Bruner DW. Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy. Gynecol Oncol. 2019 Jul;154(1):183-188. doi: 10.1016/j.ygyno.2019.04.682. Epub 2019 May 16.
PMID: 31104905RESULTKlopp AH, Yeung AR, Deshmukh S, Gil KM, Wenzel L, Westin SN, Gifford K, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Pugh SL, Kachnic LA, Bruner DW. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018 Aug 20;36(24):2538-2544. doi: 10.1200/JCO.2017.77.4273. Epub 2018 Jul 10.
PMID: 29989857RESULTYeung AR, Deshmukh S, Klopp AH, Gil KM, Wenzel L, Westin SN, Konski AA, Gaffney DK, Small W Jr, Thompson JS, Doncals DE, Cantuaria GHC, D'Souza DP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Pugh SL, Kachnic LA, Bruner DW. Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial. J Clin Oncol. 2022 Sep 20;40(27):3115-3119. doi: 10.1200/JCO.21.02831. Epub 2022 Aug 12.
PMID: 35960897DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Some outcome measures were analyzed at a later time ("\[later analysis\]") and included a patient initially considered to be ineligible (protocol violation), but later deemed eligible, thus resulting in an additional participant for these results.
Results Point of Contact
- Title
- Wendy Seiferheld, M.S.
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Ann Klopp, MD, PhD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2012
First Posted
August 27, 2012
Study Start
November 1, 2012
Primary Completion
December 1, 2015
Study Completion
May 20, 2022
Last Updated
June 15, 2022
Results First Posted
January 23, 2018
Record last verified: 2022-05