Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy

Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Adjuvant Chemotherapy in High-Risk Patients With Early-Stage Cervical Carcinoma Following Radical Hysterectomy

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without additional chemotherapy in treating cervical cancer.

PURPOSE: This randomized phase III trial is studying chemotherapy and pelvic radiation therapy to see how well they work when given with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: cisplatin; Radiation: intensity-modulated radiation therapy; Radiation: standard external beam radiation therapy; Radiation: Optional brachytherapy boost; Drug: carboplatin; Drug: paclitaxel

Detailed Description

OBJECTIVES:

Primary

• To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.

Secondary

• To evaluate adverse events.
• To evaluate overall survival.
• To evaluate quality of life.
• To evaluate chemotherapy-induced neuropathy.
• To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control.
• To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival.
• To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.

NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.

• Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.

Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.

After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
• Hong Kong
  • Chai Wan, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
• South Korea
  • Seoul, South Korea, 110-744
    • Seoul National University Hospital
  • Seoul, South Korea, 135-720
    • Gangnam Severance Hospital
  • Seoul, South Korea, 139-706
    • Korea Cancer Center Hospital
  • Kyeonggi-do
    • Seongnam, Kyeonggi-do, South Korea, 463-707
      • Seoul National University Bundang Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36608
      • Providence Hospital
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Arizona Center for Cancer Care-Peoria
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Orange, California, United States, 92868
      • Saint Joseph Hospital - Orange
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Sacramento, California, United States, 95819
      • Mercy General Hospital Radiation Oncology Center
    • Sacramento, California, United States, 95816
      • Mercy Cancer Center
    • San Diego, California, United States, 92103
      • University of California at San Diego
    • St. Helena, California, United States, 94574
      • Saint Helena Hospital
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System - Joe DiMaggio Children's Hospital
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital-Holtz Children's Hospital
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31403
      • Memorial Health University Medical Center
    • Savannah, Georgia, United States, 31405
      • Saint Joseph's-Candler Health System
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Beech Grove, Indiana, United States, 46107
      • Saint Francis Hospital and Health Centers
    • Hammond, Indiana, United States, 46320
      • Franciscan Saint Margaret Health-Hammond Campus
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Saint Francis Health-Indianapolis
    • Mishawaka, Indiana, United States, 46545-1470
      • Michiana Hematology Oncology PC-Mishawaka
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Mason City, Iowa, United States, 50401
      • Mercy Medical Center - North Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Centers-Southwest
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Center - South
    • Kansas City, Missouri, United States, 64154
      • Kansas City Cancer Centers - North
    • Lee's Summit, Missouri, United States, 64064
      • Kansas City Cancer Center-Lee's Summit
    • Rolla, Missouri, United States, 65401
      • Phelps County Regional Medical Center
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • St Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • The Nebraska Medical Center
  • New Hampshire
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • Newark, New Jersey, United States, 07103
      • UMDNJ - New Jersey Medical School
    • Voorhees Township, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper-Voorhees
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • The Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Division
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • Barberton, Ohio, United States, 44203
      • Summa Barberton Hospital
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Medina, Ohio, United States, 44256
      • Summa Health Center at Lake Medina
    • Orange, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Ravenna, Ohio, United States, 44266
      • Robinson Radiation Oncology
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
    • Sandusky, Ohio, United States, 44870
      • Ireland Cancer Center at Firelands Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center-Oncology Clinic
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Methodist Hospital
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • St. George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous, adenosquamous, or adenocarcinoma of the cervix with any/all of the following high-risk features after surgery:

  • Positive pelvic nodes
  • Positive parametrium

  • Positive para-aortic nodes that have been completely resected and are positron emission tomography (PET)/computed tomography (CT) scan-negative

    • PET only required if positive para-aortic nodes during surgery
• Clinical stage IA2, IB, or IIA disease (this corresponds to surgical tumor node metastasis (TNM) staging of T1-T2, N1, M0)

• Must have undergone radical hysterectomy (open, laparoscopically, or robotic) and staging within the past 70 days

  • Para-aortic and pelvic node sampling required

    • If the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a PET-CT is recommended, but not required
    • A negative pre- or post-operative PET scan or PET-CT scan of the para-aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection
  • No gross residual disease
• No neuroendocrine histology
• No distant metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,800/mm³
• Platelets ≥ 100,000/mm³
• White blood cell count (WBC) ≥ 4,000/mm³
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• Serum creatinine ≤ 1.5 mg/dL
• Bilirubin ≤ 1.5 times upper limit of normal
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) normal
• Alkaline phosphatase normal
• Known HIV positivity allowed provided cluster of differentiation 4 (CD4) count is ≥ 350/mm³ within the past 14 days
• No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

• No severe, active co-morbidity, including any of the following:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
  • Coagulation defects
• No prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy for the current cervical cancer

  • Prior chemotherapy for a different cancer is allowed
• No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I: Cisplatin/Radiation Therapy; Standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks as 45 Gy in 25 fractions or 50.4 Gy in 28 fractions (1.8 Gy/fraction). Concurrent cisplatin IV over one hour once weekly for 6 weeks as 40 mg/m^2, maximum dose 70 mg. A brachytherapy boost following radiation therapy is optional.	Drug: cisplatin; Intravenously; Radiation: intensity-modulated radiation therapy; Daily fractions; Other Names: IMRT; Radiation: standard external beam radiation therapy; Daily fractions; Other Names: EBRT; Radiation: Optional brachytherapy boost; Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.
Experimental: Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel; Chemoradiotherapy as in arm I, followed 4-6 weeks later by paclitaxel IV [135 mg/m2, with maximum body surface area (BSA) of 2.0 m^2 over 3 hours] and carboplatin IV [area under the curve (AUC) 5 over 30 minutes] on day 1 of 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity.	Drug: cisplatin; Intravenously; Radiation: intensity-modulated radiation therapy; Daily fractions; Other Names: IMRT; Radiation: standard external beam radiation therapy; Daily fractions; Other Names: EBRT; Radiation: Optional brachytherapy boost; Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.; Drug: carboplatin; Intravenously; Drug: paclitaxel; Intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival (Percentage of Participants Alive Without Disease)	Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.	From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (Percentage of Participants Alive)	Overall survival is estimated by the Kaplan-Meier method. The distribution of survival estimates between the two arms is compared using the log rank test. Survival time is measured from the date of randomization to the date of death from any cause or last known follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.	From randomization to death or last follow-up. Maximum follow-up time at time of analysis was 12.8 years. The 2- and 4-year survival estimates are reported.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months	The FACT-GOG/NTX4 measures patient-reported symptoms of chemotherapy-induced peripheral neuropathy in cancer patients. Possible scores range from 0 to 16 with higher scores indicating a better condition. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.	Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months	The diarrhea-specific subscore of the FACIT-D measures patient-reported diarrhea symptoms. Possible scores range from 0 to 44 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.	Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months	The cervical cancer subscore of the FACT-Cx measures patient-reported symptoms and problems related to cervical cancer. Possible scores range from 0 to 60 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.	Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Number of Participants by Highest Grade Adverse Event Reported	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years.
Associations Between Tumor Molecular Signatures, From Fixed Tissue, and Outcomes Such as Adverse Events, Disease Free Survival and Overall Survival		From randomization to last follow-up
Associations Between Secreted Factors From Serum and Plasma With Adverse Events or Outcome		From randomization to last follow-up.
Associations Between Single Nucleotide Polymorphisms (SNPs) in Genes From Buffy Coat and a Genetic Predisposition to Tumor Formation Itself or a Response to Cytotoxic Therapy		From randomization to last follow-up.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity	NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.	From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.
Disease-free Survival (Percentage of Participants Alive Without Disease) by Race	NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.	From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Anuja Jhingran, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: September 18, 2009
• First Submitted That Met QC Criteria: September 18, 2009
• First Posted (Estimated): September 21, 2009

Study Record Updates

• Last Update Posted (Estimated): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cervical squamous cell carcinoma; stage IB cervical cancer; stage IIA cervical cancer; stage IA cervical cancer; cervical adenocarcinoma; cervical adenosquamous cell carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Organic Chemicals; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Carboplatin; Paclitaxel; Cisplatin; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: RTOG-0724; CDR0000654709; NCI-2011-01973 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RTOG 0724/GOG-0724 (Other Identifier: NRG Oncology)