Bevacizumab Plus Ixabepilone to Treat Patients With Advanced Kidney Cancer
- Bevacizumab (Avastin) belongs to a class of drugs that interferes with the formation of new blood vessels. As tumors grow, they need to supply themselves with blood in order to survive and grow. Bevacizumab can reduce the amount of new blood vessels being formed to supply nutrients to tumors, and has demonstrated a significant activity in kidney cancer.
- Ixabepilone is a member of the class of drugs called epothilones. These drugs interfere with the ability of cancer cells to replicate. They have a similar mechanism of action to taxanes, another class of drugs that includes the drug Taxol, which is used to treat a variety of cancers.
- Ixabepilone can work in cells that are resistant to Taxol and has been approved to treat breast cancer that has spread beyond the breast to other parts of the body.
- To determine whether the combination of ixabepilone and bevacizumab is effective for treating kidney cancer.
- Patients 18 years of age or older with advanced kidney cancer that does not respond to standard treatments.
- Patients receive bevacizumab intravenously (through a vein) on day 1 of each 21-day treatment cycle. Ixabepilone is infused over 60 minutes on days 1-5 of each cycle. The number of cycles patients receive depends on their response to the treatment.
- Patients have CT scans and other tests before starting treatment and then at every other treatment cycle to determine the response of the tumor to treatment.
- Patients who can undergo a tumor biopsy (removal of a sample of tumor tissue) are asked to have a biopsy done before starting treatment with the study drugs and again after the first treatment cycle is completed and before the second cycle begins. This procedure is optional.
- Patients have routine and research blood tests and MRI scans.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Multi-Center Study of Bevacizumab in Combination With Ixabepilone in Subjects With Advanced Renal Cell Carcinoma|
- Response rate per RECIST. [ Time Frame: Two Years ] [ Designated as safety issue: No ]
- Determine progression-free survival [ Time Frame: Two Years ] [ Designated as safety issue: No ]
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC [ Time Frame: Two Years ] [ Designated as safety issue: Yes ]
- Determine changes in biomarkers and evaluate correlation with clinical outcomes [ Time Frame: Two Years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
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/m2/day
Bevacizumab will be administered intravenously every 3 weeks on an outpatient basis with the exception of admissions for the purpose of facilitating research studies. The dose of bevacizumab to be given is 15 mg/kg.Drug: Ixabepilone
Ixabepilone will be given on a days 1, 2, 3, 4, and 5 of each three week cycle as a one hour intravenous infusion. The dose will be 6 mg/m2/day on five successive days.
- 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. Ixabepilone is currently being evaluated in a Phase II study (CCR/NCI, Tito Fojo MD, PhD, PI) in stage IV renal carcinoma, with encouraging preliminary activity.
- 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.
- 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.
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, NCI or the Medical University of South Carolina..
- Presence of metastatic renal carcinoma, after progression or intolerance to VEGFR inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
- 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). 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00923130
|Contact: Maureen E Edgerly, R.N.||(301) firstname.lastname@example.org|
|Contact: Antonio T Fojo, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, South Carolina|
|University of South Carolina||Recruiting|
|Charlestown, South Carolina, United States, 29425|
|Principal Investigator:||Antonio T Fojo, M.D.||National Cancer Institute (NCI)|