Bevacizumab Plus Ixabepilone to Treat Patients With Advanced Kidney Cancer
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Bevacizumab; Ixabepilone
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Ixabepilone will be given on days 1, 2, 3, 4, and 5 of each three week cycle as a one hour intravenous infusion. The dose will be 6 mg/m(2)/day on five successive days.
Other intervention name(s): Avastin; Ixempra
Intervention MeSH terms: Bevacizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Renal Cell Carcinoma; Bevacizumab; Ixabepilone; Phase II