Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer
- Conditions
- Cervical Squamous Cell Carcinoma, Not Otherwise SpecifiedStage IB Cervical Cancer AJCC v6 and v7Cervical Adenosquamous CarcinomaStage IIB Cervical Cancer AJCC v6 and v7Stage III Cervical Cancer AJCC v6 and v7Cervical AdenocarcinomaStage IIA Cervical Cancer AJCC v7
- Interventions
- Biological: BevacizumabDrug: CisplatinRadiation: External Beam Radiation TherapyRadiation: Internal Radiation Therapy
- Registration Number
- NCT00369122
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial is studying how well giving bevacizumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of cervical cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and cisplatin may kill more tumor cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine treatment-related serious adverse-event rates and adverse-event rates within the first 90 days from treatment start in patients with previously untreated locally advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic radiotherapy.
SECONDARY OBJECTIVES:
I. Evaluate treatment-related serious adverse events and adverse events at any time.
II. Evaluate disease-free survival (local, regional, or distant failure, or death due to any cause).
III. Evaluate overall survival (death due to any cause). IV. Implement the image-based brachytherapy guidelines proposed by the Transatlantic Image-Guided Brachytherapy Working Group.
V. Collect CT scan or MRI-based dosimetry of brachytherapy applications used during the course of treatment for later analysis of feasibility and consistency as well as dose/volume assessments of tumor control and complications.
OUTLINE: This is a multicenter study.
Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5 weeks for a total of 45 Gy.
Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
After completion of study treatment, patients are followed periodically.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 60
-
Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix, meeting 1 of the following stage criteria:
- Stage IIB-IIIB lymph nodes
- Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size >= 5 cm
-
No positive para-aortic lymph nodes
-
Zubrod performance status 0-2
-
WBC >= 3,000/mm^3
-
Absolute granulocyte count >= 1,500/mm^3
-
Platelet count >= 100,000/mm^3
-
INR < 1.5
-
Total bilirubin =< 1.5 mg/dL
-
Serum creatinine =< 1.5 mg/dL
-
AST and ALT =< 2.5 times upper limit of normal (ULN)
-
Serum calcium =< 1.3 times ULN
-
Hemoglobin >= 10 g/dL (transfusion allowed)
-
Urine protein:creatinine ratio ? 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
None of the following illnesses or conditions:
- Medical illness preventing the use of full-dose chemotherapy
- Evidence of bleeding diathesis or coagulopathy
- Prior medical or psychiatric illness that would prevent informed consent or limit survival to < 6 months
- History of aneurysms, cerebrovascular accident, or arteriovenous malformations
- Active gastrointestinal (GI) ulcers, GI bleeding, or active inflammatory bowel disease
- Serious, nonhealing wound, ulcer, or current healing fracture
- History of any type of fistula or GI perforation
- Intra-abdominal abscess within the past 6 months
-
No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free for >= 3 years
-
No significant traumatic injury within the past 28 days
-
No clinically significant cardiovascular disease, such as the following:
- Uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)
- Myocardial infarction within the past 12 months
- Unstable angina within the past 12 months
- New York Heart Association class II-IV congestive heart failure
- Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)
- Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
-
Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
-
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
-
No known HIV
-
No prior organ transplant
-
No prior surgery for carcinoma of the cervix other than biopsy
-
No prior surgical debulking of pelvic or para-aortic nodes
-
No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding
-
No prior systemic chemotherapy
-
No major surgical procedure or open biopsy within the past 28 days or anticipation of need for major surgical procedure during the course of the study
-
No fine needle aspirations or core biopsies within the past 7 days
-
No concurrent major surgical procedure
-
No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)
-
No concurrent intensity-modulated radiotherapy
-
No concurrent transvaginal irradiation to control bleeding
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (radiation therapy, bevacizumab, cisplatin) External Beam Radiation Therapy Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35. Treatment (radiation therapy, bevacizumab, cisplatin) Internal Radiation Therapy Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35. Treatment (radiation therapy, bevacizumab, cisplatin) Bevacizumab Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35. Treatment (radiation therapy, bevacizumab, cisplatin) Cisplatin Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
- Primary Outcome Measures
Name Time Method Number of Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start. From start of treatment to 90 days. Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Grade (Gr) \>= 4 vaginal bleeding, Gr \>=4 thrombotic event, Gr \>=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for \>2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for \>7 days, febrile neutropenia defined as a temperature \>38.5 degree Celsius and granulocytes \< 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.
- Secondary Outcome Measures
Name Time Method Overall Survival (Three-year Rate Reported) From registration to 3 years Overall survival time is defined as time from registration to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time. From start of treatment to last follow-up, up to 6.0 years. Analysis occurred after all patients had been on study for at least 2 years. Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Gr \>= 4 vaginal bleeding, Gr \>=4 thrombotic event, Gr \>=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for \>2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for \>7 days, febrile neutropenia defined as a temperature \>38.5 degree Celsius and granulocytes \< 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.
Disease-free Survival (Three-year Rate Reported) From registration to 3 years Failure is defined as local, regional, or distant disease, or death due to any cause. Disease-free survival time is defined as time from registration to the date of failure and disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive and disease-free are censored at the date of last contact.
Trial Locations
- Locations (106)
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Integrated Community Oncology Network-Florida Cancer Center Beaches
🇺🇸Jacksonville Beach, Florida, United States
University of Florida Health Science Center - Jacksonville
🇺🇸Jacksonville, Florida, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Integrated Community Oncology Network-Southside Cancer Center
🇺🇸Jacksonville, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Baptist Medical Center South
🇺🇸Jacksonville, Florida, United States
Bay Medical Center
🇺🇸Panama City, Florida, United States
Integrated Community Oncology Network-Flager Cancer Center
🇺🇸Saint Augustine, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Northwest Community Hospital
🇺🇸Arlington Heights, Illinois, United States
Franciscan St. James Health-Olympia Fields Campus
🇺🇸Olympia Fields, Illinois, United States
Saint Vincent Anderson Regional Hospital/Cancer Center
🇺🇸Anderson, Indiana, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Franciscan Saint Francis Health-Beech Grove
🇺🇸Beech Grove, Indiana, United States
Providence Medical Center
🇺🇸Kansas City, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Norton Suburban Hospital and Medical Campus
🇺🇸Louisville, Kentucky, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Cape Radiation Oncology
🇺🇸Cape Girardeau, Missouri, United States
Centerpoint Medical Center LLC
🇺🇸Independence, Missouri, United States
Radiation Oncology Practice Corporation South
🇺🇸Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Radiation Oncology Practice Corporation - North
🇺🇸Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Liberty Radiation Oncology Center
🇺🇸Liberty, Missouri, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Highland Hospital
🇺🇸Rochester, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸Akron, Ohio, United States
Summa Barberton Hospital
🇺🇸Barberton, Ohio, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Samaritan North Health Center
🇺🇸Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Veteran Affairs Medical Center
🇺🇸Dayton, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Cancer Care Center, Incorporated
🇺🇸Salem, Ohio, United States
Clinton Memorial Hospital
🇺🇸Wilmington, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Einstein Medical Center Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, United States
Main Line Health NCORP
🇺🇸Wynnewood, Pennsylvania, United States
American Fork Hospital / Huntsman Intermountain Cancer Center
🇺🇸American Fork, Utah, United States
Cottonwood Hospital Medical Center
🇺🇸Murray, Utah, United States
Sandra L Maxwell Cancer Center
🇺🇸Cedar City, Utah, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Logan Regional Hospital
🇺🇸Logan, Utah, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸Yakima, Washington, United States
Southwest VA Regional Cancer Center
🇺🇸Norton, Virginia, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
McGill University Department of Oncology
🇨🇦Montreal, Quebec, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Northwestern University
🇺🇸Chicago, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Intermountain Health Care
🇺🇸Salt Lake City, Utah, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸Salt Lake City, Utah, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Shawnee Mission Medical Center-KCCC
🇺🇸Shawnee Mission, Kansas, United States
Saint Luke's South Hospital
🇺🇸Overland Park, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Radiation Oncology Practice Corporation Southwest
🇺🇸Overland Park, Kansas, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Wright-Patterson Medical Center
🇺🇸Wright-Patterson Air Force Base, Ohio, United States
University of Colorado
🇺🇸Denver, Colorado, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Wellmont Holston Valley Hospital and Medical Center
🇺🇸Kingsport, Tennessee, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Reid Health
🇺🇸Richmond, Indiana, United States
Dixie Medical Center Regional Cancer Center
🇺🇸Saint George, Utah, United States
21st Century Oncology-Orange Park
🇺🇸Orange Park, Florida, United States
21st Century Oncology-Palatka
🇺🇸Palatka, Florida, United States