Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy
- Conditions
- Cervical Cancer
- Interventions
- Radiation: intensity-modulated radiation therapyRadiation: standard external beam radiation therapyRadiation: Optional brachytherapy boost
- Registration Number
- NCT00980954
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 236
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I: Cisplatin/Radiation Therapy cisplatin 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. Arm I: Cisplatin/Radiation Therapy intensity-modulated 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. Arm I: Cisplatin/Radiation Therapy standard external beam 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. Arm I: Cisplatin/Radiation Therapy Optional brachytherapy boost 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel carboplatin 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel cisplatin 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel intensity-modulated radiation therapy 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel standard external beam radiation therapy 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. Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel Optional brachytherapy boost 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.
- Primary Outcome Measures
Name Time Method Disease-free Survival (Percentage of Participants Alive Without Disease) 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 (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.
- Secondary Outcome Measures
Name Time Method Overall Survival (Percentage of Participants Alive) 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. 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.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) 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.
Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) 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.
Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) 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.
Number of Participants by Highest Grade Adverse Event Reported From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years. 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.
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.
Trial Locations
- Locations (125)
Grady Health System
🇺🇸Atlanta, Georgia, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
Jackson Memorial Hospital-Holtz Children's Hospital
🇺🇸Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Saint Joseph Hospital - Orange
🇺🇸Orange, California, United States
Providence Hospital
🇺🇸Mobile, Alabama, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Franciscan Saint Margaret Health-Hammond Campus
🇺🇸Hammond, Indiana, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Saint Alphonsus Regional Medical Center
🇺🇸Boise, Idaho, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Saint Francis Hospital and Health Centers
🇺🇸Beech Grove, Indiana, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Hickman Cancer Center
🇺🇸Adrian, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Robinson Radiation Oncology
🇺🇸Ravenna, Ohio, United States
Central Maryland Radiation Oncology in Howard County
🇺🇸Columbia, Maryland, United States
Phelps County Regional Medical Center
🇺🇸Rolla, Missouri, United States
Summa Barberton Hospital
🇺🇸Barberton, Ohio, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Summa Health Center at Lake Medina
🇺🇸Medina, Ohio, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸Voorhees, New Jersey, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
UMDNJ - New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Women and Infants Hospital
🇺🇸Providence, Rhode Island, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Orange Village, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸Westlake, Ohio, United States
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
State University of New York Downstate Medical Center
🇺🇸Brooklyn, New York, United States
Kansas City Cancer Center-Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Delaware County Memorial Hospital
🇺🇸Drexel Hill, Pennsylvania, United States
Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸Akron, Ohio, United States
Elliot Hospital
🇺🇸Manchester, New Hampshire, United States
University of Rochester
🇺🇸Rochester, New York, United States
Dixie Medical Center Regional Cancer Center
🇺🇸Saint George, Utah, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸Yakima, Washington, United States
Cancer Care Center, Incorporated
🇺🇸Salem, Ohio, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Sanford Cancer Center-Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Wheeling Hospital
🇺🇸Wheeling, West Virginia, United States
University of Tennessee - Knoxville
🇺🇸Knoxville, Tennessee, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Korea Cancer Center Hospital
🇰🇷Seoul, Korea, Republic of
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
University of California At San Diego
🇺🇸San Diego, California, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Kansas City Cancer Centers-Southwest
🇺🇸Overland Park, Kansas, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
McGill University Department of Oncology
🇨🇦Montreal, Quebec, Canada
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
The Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Pomona Valley Hospital Medical Center
🇺🇸Pomona, California, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Arizona Center for Cancer Care-Peoria
🇺🇸Peoria, Arizona, United States
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Saint Helena Hospital
🇺🇸Saint Helena, California, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Saint Joseph's-Candler Health System
🇺🇸Savannah, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Saint Vincent Anderson Regional Hospital/Cancer Center
🇺🇸Anderson, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Franciscan Saint Francis Health-Indianapolis
🇺🇸Indianapolis, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Mercy Medical Center - North Iowa
🇺🇸Mason City, Iowa, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Saint John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
🇺🇸Mount Holly, New Jersey, United States
Highland Hospital
🇺🇸Rochester, New York, United States
Akron General Medical Center
🇺🇸Akron, Ohio, United States
Ireland Cancer Center at Firelands Regional Medical Center
🇺🇸Sandusky, Ohio, United States
Flower Hospital
🇺🇸Sylvania, Ohio, United States
Seoul National University Bundang Hospital
🇰🇷Seongnam City, Kyeonggi-do, Korea, Republic of
Aurora West Allis Medical Center
🇺🇸West Allis, Wisconsin, United States
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Southern Ohio Medical Center
🇺🇸Portsmouth, Ohio, United States
Mercy Cancer Center
🇺🇸Sacramento, California, United States
Mercy General Hospital Radiation Oncology Center
🇺🇸Sacramento, California, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Kansas City Cancer Center - South
🇺🇸Kansas City, Missouri, United States
Kansas City Cancer Centers - North
🇺🇸Kansas City, Missouri, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Montefiore Medical Center-Weiler Division
🇺🇸Bronx, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Pamela Youde Nethersole Eastern Hospital
ðŸ‡ðŸ‡°Chai Wan, Hong Kong