A Phase II Study of Postoperative Intensity Modulated Radiation Therapy (IMRT) With Concurrent Cisplatin and Bevacizumab Followed by Carboplatin and Paclitaxel for Patients With Endometrial Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Endometrial Adenocarcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 34
- Locations
- 41
- Primary Endpoint
- Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase II trial studies the side effects of giving intensity-modulated radiation therapy together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how well they work in treating patients who have undergone surgery for high-risk endometrial cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving intensity-modulated radiation therapy together with chemotherapy and bevacizumab after surgery may kill any tumor cells that remain after surgery.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the treatment-related, grade 3+, non-hematologic adverse-event rate within 90 days from the start of treatment with concurrent intensity-modulated radiotherapy, cisplatin, and bevacizumab followed by carboplatin and paclitaxel in patients with high-risk endometrial cancer. SECONDARY OBJECTIVES: I. To evaluate treatment-related adverse events occurring within 1 year from the start of treatment. II. To evaluate all treatment-related adverse events. III. To evaluate disease-free and overall survival. IV. To evaluate local, regional, and distant failure. OUTLINE: Patients undergo pelvic intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin intravenously (IV) over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed endometrial cancer, including 1 of the following cellular types:
- •Endometrioid endometrial adenocarcinoma
- •Clear cell carcinoma
- •Papillary serous adenocarcinoma
- •Adenosquamous cell carcinoma
- •Other adenocarcinoma variant
- •No carcinosarcoma
- •Meets 1 of the following criteria:
- •Grade 3 carcinoma with \> 50% myometrial invasion (stage IC or IIA) (all papillary serous or clear cell carcinoma will be considered grade 3)
- •Grade 2 or 3 carcinoma with any cervical stromal invasion (stage IIB)
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)
Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)
Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)
Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)
Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Intensity-Modulated Radiation Therapy
Treatment (IMRT, cisplatin,bevacizumab,carboplatin,paclitaxel)
Patients undergo pelvic IMRT once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start
Time Frame: From start of treatment to 90 days
Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Secondary Outcomes
- Treatment-related Grade 3+ Adverse Events(From start of treatment to end of follow-up, up to 43.4 months; analysis occurred after all patients had been on study for at least one year.)
- Overall Survival (Two-year Rate Reported)(From registration to two years)
- Disease-free Survival (Two-year Rate Reported)(From registration to two years)
- Pelvic Failure Rate (Two-year Rate Reported)(From registration to two years)
- Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 1 Year After Treatment Start(From start of treatment to one year)
- Distant Failure (Two-year Rate Reported)(From registration to two years)