Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer
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| ClinicalTrials.gov Identifier: NCT00369122 |
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Recruitment Status :
Completed
First Posted : August 29, 2006
Results First Posted : May 17, 2013
Last Update Posted : March 20, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Biological: Bevacizumab Drug: Cisplatin Radiation: External Beam Radiation Therapy Radiation: Internal Radiation Therapy | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 60 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA |
| Actual Study Start Date : | August 11, 2006 |
| Actual Primary Completion Date : | June 4, 2010 |
| Actual Study Completion Date : | December 15, 2016 |
| Arm | Intervention/treatment |
|---|---|
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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. |
Biological: Bevacizumab
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Internal Radiation Therapy Undergo brachytherapy
Other Names:
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- 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.
- 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.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00369122
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| Principal Investigator: | Tracey Schefter | Radiation Therapy Oncology Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00369122 |
| Obsolete Identifiers: | NCT01530633 |
| Other Study ID Numbers: |
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 ) |
| First Posted: | August 29, 2006 Key Record Dates |
| Results First Posted: | May 17, 2013 |
| Last Update Posted: | March 20, 2018 |
| Last Verified: | February 2018 |
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Carcinoma Carcinoma, Squamous Cell Uterine Cervical Neoplasms Carcinoma, Adenosquamous Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Uterine Cervical Diseases Uterine Diseases Genital Diseases, Female |
Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Diseases Neoplasms, Complex and Mixed Bevacizumab Antineoplastic Agents, Immunological Cisplatin Endothelial Growth Factors Antibodies Immunoglobulins Antibodies, Monoclonal Immunoglobulin G Antineoplastic Agents Angiogenesis Inhibitors |