A Phase II Multi-Center Study of Bevacizumab in Combination With Ixabepilone in Subjects With Advanced Renal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Renal Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Progression-free Survival
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
Background:
- Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib).
- Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans.
- Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma.
- Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities.
- Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable.
Primary Objectives:
- Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC.
- Determine progression-free survival.
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC.
- Determine changes in biomarkers and evaluate correlation with clinical outcomes.
Eligibility:
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina.
- Presence of metastatic renal carcinoma, after progression or intolerance to Vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
Design:
- Multi-center, open labeled phase II study
- Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued.
- Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2).
- In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
Detailed Description
Background: * Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib). * Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans. * Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma. * Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities. * Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable. Primary Objectives: * Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC. * Determine progression-free survival. * Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC. * Determine changes in biomarkers and evaluate correlation with clinical outcomes. Eligibility: * Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina. * Presence of metastatic renal carcinoma, after progression or intolerance to vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib). * Adequate organ and bone marrow function. Design: * Multi-center, open labeled phase II study * Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued. * Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2). * In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
Investigators
Ravi A. Madan, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Bevacizumab with Ixabepilone
Bevacizumab 15mg/kg every 3 weeks Ixabepilone given on days 1,2,3,4 and 5 of each three week cycle at a dose of 6mg/m(2)/day
Intervention: Bevacizumab
Bevacizumab with Ixabepilone
Bevacizumab 15mg/kg every 3 weeks Ixabepilone given on days 1,2,3,4 and 5 of each three week cycle at a dose of 6mg/m(2)/day
Intervention: Ixabepilone
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: up to 44 months
The time between the first day of treatment to the day of disease progression. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Secondary Outcomes
- Number of Participants With an Objective Response (Complete Response (CR) or Partial Response (PR)) Per the Response Evaluation Criteria in Solid Tumors (RECIST)(Two Years)
- Number of Participants With Adverse Events(Date treatment consent signed to date off study, approximately 84 months and 25 days)
- Number of Participants Who Had Biopsies(Baseline and Cycle 2 Day 1)
- Overall Survival(Time between the first day of treatment and the day of death, assessed up to approximately 7 years.)