Clinical Trial: Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief Summary: This phase II trial is studying the side effects of giving intensity-modulated radiation therapy together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how well it works 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 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 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 Summary:

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: This is a multicenter study.

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 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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: From start of treatment to 90 days ]

The rate of the acute specified AEs (adverse events) from previous Radiation Therapy Oncology Group (RTOG) trial 9708 (RT + cisplatin) was 44% and the hypothesis is that the addition of bevacizumab to IMRT + cisplatin will not increase this rate beyond 60%. This study was designed with a 1-sided, upper bound confidence interval to estimate this AE rate. Twenty-seven evaluable patients were required to have 95% confidence that the true grade 3+ non-hematologic treatment-related AE rate is not greater than 60%. Please note that this is a 95% ONE-SIDED confidence bound which is equivalent to the upper bound of a two-sided 90% confidence interval.


Original Primary Outcome: Treatment-related, grade 3+, non-hematologic adverse events occurring within 90 days after the start of treatment as assessed by NCI CTCAE v4.0

Current Secondary Outcome:

  • Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of treatment to one year ]
  • Percentage of Participants With Treatment-related Adverse Events as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of treatment to end of follow-up ]
  • Overall Survival [ Time Frame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ]
    Will be estimated using the Kaplan-Meier method.
  • Disease-free Survival [ Time Frame: From registration to date of first failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ]
    Will be estimated using the Kaplan-Meier method.
  • Pelvic Failure [ Time Frame: From registration to date of pelvic failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ]
    Will be estimated using the cumulative incidence method.
  • Distant Failure [ Time Frame: From registration to date of distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ]
    Will be estimated using the cumulative incidence method.


Original Secondary Outcome:

  • Treatment-related, grade 3+, non-hematologic adverse events occurring within 1 year after the start of treatment as assessed by NCI CTCAE v4.0
  • All Treatment-related Adverse Events as Assessed by NCI CTCAE v4.0
  • Overall Survival
  • Progression-free survival
  • Pelvic Failure
  • Distant Failure


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 29, 2009
Date Started: November 2009
Date Completion:
Last Updated: October 9, 2014
Last Verified: June 2014