A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Cervical Adenocarcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 60
- Locations
- 106
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Bevacizumab
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.
Intervention: Cisplatin
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.
Intervention: External Beam Radiation Therapy
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.
Intervention: Internal Radiation Therapy
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Survival (Three-year Rate Reported)(From registration to 3 years)
- 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.)
- Disease-free Survival (Three-year Rate Reported)(From registration to 3 years)