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Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00369122
Recruitment Status : Completed
First Posted : August 29, 2006
Results First Posted : May 17, 2013
Last Update Posted : March 20, 2018
Sponsor:
Collaborator:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE August 24, 2006
First Posted Date  ICMJE August 29, 2006
Results First Submitted Date  ICMJE March 5, 2013
Results First Posted Date  ICMJE May 17, 2013
Last Update Posted Date March 20, 2018
Actual Study Start Date  ICMJE August 11, 2006
Actual Primary Completion Date June 4, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)		 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. [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time. [ Time Frame: 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) [ Time Frame: 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.
  • Overall Survival (Three-year Rate Reported) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer
Official Title  ICMJE A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma, Not Otherwise Specified
  • Stage IB Cervical Cancer AJCC v6 and v7
  • Stage IIA Cervical Cancer AJCC v7
  • Stage IIB Cervical Cancer AJCC v6 and v7
  • Stage III Cervical Cancer AJCC v6 and v7
Intervention  ICMJE
  • Biological: Bevacizumab
    Given IV
    Other Names:
    • Anti-VEGF
    • Anti-VEGF Humanized Monoclonal Antibody
    • Anti-VEGF rhuMAb
    • Avastin
    • Bevacizumab Biosimilar BEVZ92
    • Bevacizumab Biosimilar BI 695502
    • Bevacizumab Biosimilar CBT 124
    • Bevacizumab Biosimilar FKB238
    • BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED
    • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
    • Recombinant Humanized Anti-VEGF Monoclonal Antibody
    • rhuMab-VEGF
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Radiation: External Beam Radiation Therapy
    Undergo EBRT
    Other Names:
    • Definitive Radiation Therapy
    • EBRT
    • External Beam Radiotherapy
    • External Beam RT
    • external radiation
    • External Radiation Therapy
    • external-beam radiation
  • Radiation: Internal Radiation Therapy
    Undergo brachytherapy
    Other Names:
    • BRACHYTHERAPY
    • internal radiation
    • Internal Radiation Brachytherapy
    • Radiation Brachytherapy
Study Arms  ICMJE Experimental: Treatment (radiation therapy, bevacizumab, 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.

Interventions:
  • Biological: Bevacizumab
  • Drug: Cisplatin
  • Radiation: External Beam Radiation Therapy
  • Radiation: Internal Radiation Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2014)		 60
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 15, 2016
Actual Primary Completion Date June 4, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00369122
Other Study ID Numbers  ICMJE NCI-2009-00722
NCI-2009-00722 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000493005
RTOG 0417 ( Other Identifier: Radiation Therapy Oncology Group )
RTOG-0417 ( Other Identifier: CTEP )
U10CA021661 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Cancer Institute (NCI)
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE National Cancer Institute (NCI)
Original Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE Radiation Therapy Oncology Group
Investigators  ICMJE
Principal Investigator: Tracey Schefter Radiation Therapy Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP