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AzTrials

Cervical CancerPhase 3NCT01672892

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

A Phase 3 study testing Standard radiation therapy and intensity-modulated radiation therapy in people with Cervical Cancer and Endometrial Cancer, run by Radiation Therapy Oncology Group at 137 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Standard radiation therapy and intensity-modulated radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
289 participants
Where
137 sitesin 4 countries
Study dates
Nov 2012to 20 May 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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)
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  • 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:
  • 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.)
  • 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

Who cannot join

  • 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
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  • 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:
  • 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

Trial locations and contacts

137 sites in 4 countries.

137 sites in 4 countries

United States129 sites

  • Leeward Radiation Oncology Center

    ‘Ewa Beach, Hawaii, 96706

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Summa Akron City Hospital/Cooper Cancer Center

    Akron, Ohio, 44304

  • University of New Mexico

    Albuquerque, New Mexico, 87106

  • McFarland Clinic PC-William R Bliss Cancer Center

    Ames, Iowa, 50010

  • Saint Vincent Anderson Regional Hospital/Cancer Center

    Anderson, Indiana, 46016

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106-0995

  • Grady Health System

    Atlanta, Georgia, 30303

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Northside Hospital

    Atlanta, Georgia, 30342

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Summa Barberton Hospital

    Barberton, Ohio, 44203

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Sanford Clinic North-Bemidgi

    Bemidji, Minnesota, 56601

  • Billings Clinic

    Billings, Montana, 59107-7000

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Geaugra Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612-3785

  • University of Illinois

    Chicago, Illinois, 60612

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Northside Hospital-Forsyth

    Cumming, Georgia, 30041

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Franciscan Saint Margaret Health-Dyer Campus

    Dyer, Indiana, 46311

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • California Cancer Center - North Fresno

    Fresno, California, 93720

  • University of Florida

    Gainesville, Florida, 32610

  • Northeast Georgia Medical Center

    Gainesville, Georgia, 30501

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Mercy Health Saint Mary's

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311-6519

  • Self Regional Healthcare

    Greenwood, South Carolina, 29646

  • Franciscan Saint Margaret Health-Hammond Campus

    Hammond, Indiana, 46320

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Edwards Comprehensive Cancer Center

    Huntington, West Virginia, 25701

  • University of Florida Health Science Center

    Jacksonville, Florida, 32209

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Rocky Mountain Cancer Centers-Littleton

    Littleton, Colorado, 80120

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • McKee Medical Center

    Loveland, Colorado, 80539

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Summa Health Center at Lake Medina

    Medina, Ohio, 44256

  • Lake University Ireland Cancer Center

    Mentor, Ohio, 44060

  • Jackson Memorial Hospital-Holtz Children's Hospital

    Miami, Florida, 33136

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Southwest General Health Center Ireland Cancer Center

    Middleburg Heights, Ohio, 44130

  • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional

    Milford, Massachusetts, 01757

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

    Mount Holly, New Jersey, 08060

  • Intermountain Medical Center

    Murray, Utah, 84157

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • North Shore-LIJ Health System/Center for Advanced Medicine

    New Hyde Park, New York, 11040

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Saint Joseph Hospital - Orange

    Orange, California, 92868

  • UHHS-Chagrin Highlands Medical Center

    Orange, Ohio, 44122

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Feather River Cancer Center

    Paradise, California, 95969

  • Capital Health Medical Center-Hopewell

    Pennington, New Jersey, 08534

  • Radiation Therapy Oncology Group

    Philadelphia, Pennsylvania, 19103

  • Arizona Oncology-Deer Valley Center

    Phoenix, Arizona, 85027

  • Pomona Valley Hospital Medical Center

    Pomona, California, 91767

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

  • Kaiser Permanente-Rancho Cordova Cancer Center

    Rancho Cordova, California, 95670

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Rohnert Park Cancer Center

    Rohnert Park, California, 94928

  • The Permanente Medical Group-Roseville Radiation Oncology

    Roseville, California, 95678

  • University of California at Davis Cancer Center

    Sacramento, California, 95817

  • South Sacramento Cancer Center

    Sacramento, California, 95823

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Peninsula Regional Medical Center

    Salisbury, Maryland, 21801

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Saint Joseph's-Candler Health System

    Savannah, Georgia, 31405

  • Arizona Oncology Services Foundation

    Scottsdale, Arizona, 85260

  • Virginia Mason CCOP

    Seattle, Washington, 98101

  • Holy Cross Hospital

    Silver Spring, Maryland, 20910

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Kaiser Permanente Cancer Treatment Center

    South San Francisco, California, 94080

  • Dana-Farber/Brigham and Women's Cancer Center at South Shore

    South Weymouth, Massachusetts, 02190

  • D'Amour Center for Cancer Care

    Springfield, Massachusetts, 01107

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • Dixie Medical Center Regional Cancer Center

    St. George, Utah, 84770

  • Mount Nittany Medical Center

    State College, Pennsylvania, 16803

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • South Atlantic Radiation Oncology

    Supply, North Carolina, 28462

  • Virtua West Jersey Hospital Voorhees

    Voorhees Township, New Jersey, 08043

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Saint John Macomb-Oakland Hospital

    Warren, Michigan, 48093

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • UHHS-Westlake Medical Center

    Westlake, Ohio, 44145

  • Coastal Carolina Radiation Oncology

    Wilmington, North Carolina, 28401

  • New Hanover Regional Medical Center

    Wilmington, North Carolina, 28401

  • Lankenau Hospital

    Wynnewood, Pennsylvania, 19096

Other trials in United States

Canada6 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA-Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • BCCA-Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

Other trials in Canada

Hong Kong1 site

  • Pamela Youde Nethersole Eastern Hospital

    Chai Wan

Other trials in Hong Kong

Singapore1 site

  • National University Hospital

    Singapore, 119074

Other trials in Singapore

About this study

Official title: 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.

Read the 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.

Being tested
Standard radiation therapy, intensity-modulated radiation therapy
Keywords
gastrointestinal complications, perioperative/postoperative complications, radiation toxicity, urinary complications, urinary tract toxicity, endometrial clear cell carcinoma, endometrial papillary serous carcinoma, stage IA endometrial carcinoma, stage IB endometrial carcinoma, stage II endometrial carcinoma, stage IIIA endometrial carcinoma, stage IIIB endometrial carcinoma, stage IIIC endometrial carcinoma, endometrial adenocarcinoma, cervical adenocarcinoma, stage IB cervical cancer, stage IIA cervical cancer, stage IIB cervical cancer
Medical subject headings
Uterine Cervical Neoplasms, Endometrial Neoplasms, Postoperative Complications, Radiation Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard radiation therapyRadiation

    Also called RT

    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.

  • intensity-modulated radiation therapyRadiation

    Also called IMRT

    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.

Study groups in NCT01672892
Study groupRoleWhat they receive
Intensity-Modulated Radiation TherapyExperimentalintensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
Receives: Radiation: Standard radiation therapy
Standard Radiation TherapyActive comparatorStandard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy
Receives: Radiation: intensity-modulated radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and week 5 of RT

Secondary outcomes (12)

  1. Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment

    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.

    Measured: Baseline to Week 5 of RT

  2. Urinary Toxicity, as Measured by Change in EPIC Urinary Domain

    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.

    Measured: Baseline, week 3 and 5 of RT, and 4-6 weeks after RT

  3. Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale

    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.

    Measured: 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

  4. Health Utilities, as Measured by Change From Baseline in EQ-5D

    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.

    Measured: Baseline, week 5 of RT, 4-6 weeks after RT

  5. Local-regional Recurrence

    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.

    Measured: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

  6. Disease-free Survival

    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.

    Measured: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

  7. Overall Survival

    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.

    Measured: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

  8. Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers

    Measured: Outcome measure will not be analyzed

  9. Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability)

    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.

    Measured: Baseline and week 5 of RT

  10. Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence)

    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.

    Measured: Baseline and week 5 of RT

  11. Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity)

    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.

    Measured: Baseline and week 5 of RT

  12. Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment)

    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.

    Measured: Baseline and week 5 of RT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionDec 2015
  4. Study completion20 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
289 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01672892
Sponsor's protocol ID
RTOG-1203
Other IDs
CDR0000738944, NCI-2012-02001
Status last verified
May 2022
First submitted
23 Aug 2012
Last updated
15 Jun 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32073955

  • Gil 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.

    PubMed 31104905

  • Klopp 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.

    PubMed 29989857

  • Yeung 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.

    PubMed 35960897

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Standard radiation therapy and intensity-modulated radiation therapy in people with Cervical Cancer and Endometrial Cancer, run by Radiation Therapy Oncology Group at 137 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 137 sites in United States, Canada, Hong Kong, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01672892, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.

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