Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00126503
Status:
COMPLETED
Last Update Posted:
2015-01-15
First Post:
2005-08-02
Brief Title:
Sorafenib Tosylate and Bevacizumab in Treating Patients With Advanced Kidney Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase III Trial of BAY 43-9006 in Combination With Bevacizumab in Patients With Advanced Renal Cancer
Status:
COMPLETED
Status Verified Date:
2014-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the side effects and best dose of sorafenib tosylate and bevacizumab and to see how well they work in treating patients with advanced kidney cancer Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Monoclonal antibodies such as bevacizumab can block tumor growth by targeting certain cells Bevacizumab and sorafenib tosylate may also stop the growth of tumor cells by blocking blood flow to the tumor Giving sorafenib tosylate together with bevacizumab may kill more tumor cells
Detailed Description:
PRIMARY OBJECTIVES
I To determine the tolerability and maximum tolerated dose of Sorafenib sorafenib tosylate when given orally in combination with Bevacizumab in patients with renal cell carcinoma RCC Phase I II To estimate the objective response rate of advanced RCC receiving the combination therapy of Bevacizumab and Sorafenib Phase II III To estimate the progression-free survival of advanced renal cell carcinoma patients to Sorafenib sorafenib tosylate in combination with Bevacizumab Phase II
SECONDARY OBJECTIVES
I To obtain fixed tissue in the form of paraffin blocks or unstained slides for evaluation of the following von Hippel-Lindau tumor suppressor E3 ubiquitin protein ligase VHL mutation status and phosphatase and tensin homolog PTEN mutation andor expression status VHL downstream proteins Apoptosis and proliferation status Microvascular density and if able to process kinase status- phosphorylation inactive for mitogen-activated protein MAP kinase v-akt murine thymoma viral oncogene homolog 1 Akt and kinase insert domain receptor KDR if feasible
II In situations where fresh tumor may be obtained prior to andor following therapy 4 weeks
1 Assess tumor baseline and changes in signal transduction - Raf-1 proto-oncogene serinethreonine kinase Raf mitogen-activated protein kinase kinase MEK mitogen-activated protein kinase 1 Erk Erk phosphorylation Akt phosphorylation status and Raf subcellular localization
2 fms-related tyrosine kinase 1 VEGFR1 flk1 and kinase insert domain receptor VEGFR2 flt1KDR status and tissue vascular endothelial growth factor VEGF
3 Tumor cell apoptosis - marker of proliferation Ki-67 Ki-67 transferase dUTP nick end labeling TUNEL staining and expression levels of BH3 interacting domain death agonist BH3 domain containing proteins
4 Tumor blood vessel characteristics - microvessel density fraction of immature tumor blood vessels endothelial cell apoptosis
5 Presence of VHL downstream proteins III To relate changes in tumor perfusion and vascular permeability on serial arterial spin labeled ASL and dynamic contrast-enhanced DCE-magnetic resonance imaging MRI to clinical outcome and anti-tumor effects
IV Evaluate the pharmacokinetics of Sorafenib alone and in combination and bevacizumab in patients enrolled on the maximum tolerated dose MTD dose level of Sorafenib and bevacizumab representing the recommended phase II dose RPTD schedule 200mg once daily QD Sorafenib and 5 mgkg intravenously IV Q 2 weeks of bevacizumab
V To determine the steady-state trough plasma concentration of Sorafenib and trough concentration of Bevacizumab and relate to toxicity and correlative endpoints
VI Serial analysis of circulating angiogenic cytokines ie VEGF angiopoeitin 2 basic fibroblast growth factor bFGF interleukin IL-8 etc and association of findings with response response duration and prediction of relapse
OUTLINE This phase I dose-escalation study followed by a phase II study
PHASE I Patients receive sorafenib tosylate orally PO twice daily on days 1-28 and bevacizumab intravenously IV over 30-90 minutes on days 1 and 15
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of sorafenib tosylate and bevacizumab until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity An additional 6 patients are treated at the MTD
PHASE II Patients receive sorafenib tosylate PO once daily on days 1-28 and bevacizumab IV over 90 minutes on days 1 and 15 at the MTD in the absence of disease progression or unacceptable toxicity
Note Patients may remain on protocol if only 1 of the drugs is stopped
After completion of study treatment patients are followed up every 3 months for 2 years and then every 6 months thereafter
I To determine the tolerability and maximum tolerated dose of Sorafenib sorafenib tosylate when given orally in combination with Bevacizumab in patients with renal cell carcinoma RCC Phase I II To estimate the objective response rate of advanced RCC receiving the combination therapy of Bevacizumab and Sorafenib Phase II III To estimate the progression-free survival of advanced renal cell carcinoma patients to Sorafenib sorafenib tosylate in combination with Bevacizumab Phase II
SECONDARY OBJECTIVES
I To obtain fixed tissue in the form of paraffin blocks or unstained slides for evaluation of the following von Hippel-Lindau tumor suppressor E3 ubiquitin protein ligase VHL mutation status and phosphatase and tensin homolog PTEN mutation andor expression status VHL downstream proteins Apoptosis and proliferation status Microvascular density and if able to process kinase status- phosphorylation inactive for mitogen-activated protein MAP kinase v-akt murine thymoma viral oncogene homolog 1 Akt and kinase insert domain receptor KDR if feasible
II In situations where fresh tumor may be obtained prior to andor following therapy 4 weeks
1 Assess tumor baseline and changes in signal transduction - Raf-1 proto-oncogene serinethreonine kinase Raf mitogen-activated protein kinase kinase MEK mitogen-activated protein kinase 1 Erk Erk phosphorylation Akt phosphorylation status and Raf subcellular localization
2 fms-related tyrosine kinase 1 VEGFR1 flk1 and kinase insert domain receptor VEGFR2 flt1KDR status and tissue vascular endothelial growth factor VEGF
3 Tumor cell apoptosis - marker of proliferation Ki-67 Ki-67 transferase dUTP nick end labeling TUNEL staining and expression levels of BH3 interacting domain death agonist BH3 domain containing proteins
4 Tumor blood vessel characteristics - microvessel density fraction of immature tumor blood vessels endothelial cell apoptosis
5 Presence of VHL downstream proteins III To relate changes in tumor perfusion and vascular permeability on serial arterial spin labeled ASL and dynamic contrast-enhanced DCE-magnetic resonance imaging MRI to clinical outcome and anti-tumor effects
IV Evaluate the pharmacokinetics of Sorafenib alone and in combination and bevacizumab in patients enrolled on the maximum tolerated dose MTD dose level of Sorafenib and bevacizumab representing the recommended phase II dose RPTD schedule 200mg once daily QD Sorafenib and 5 mgkg intravenously IV Q 2 weeks of bevacizumab
V To determine the steady-state trough plasma concentration of Sorafenib and trough concentration of Bevacizumab and relate to toxicity and correlative endpoints
VI Serial analysis of circulating angiogenic cytokines ie VEGF angiopoeitin 2 basic fibroblast growth factor bFGF interleukin IL-8 etc and association of findings with response response duration and prediction of relapse
OUTLINE This phase I dose-escalation study followed by a phase II study
PHASE I Patients receive sorafenib tosylate orally PO twice daily on days 1-28 and bevacizumab intravenously IV over 30-90 minutes on days 1 and 15
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of sorafenib tosylate and bevacizumab until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity An additional 6 patients are treated at the MTD
PHASE II Patients receive sorafenib tosylate PO once daily on days 1-28 and bevacizumab IV over 90 minutes on days 1 and 15 at the MTD in the absence of disease progression or unacceptable toxicity
Note Patients may remain on protocol if only 1 of the drugs is stopped
After completion of study treatment patients are followed up every 3 months for 2 years and then every 6 months thereafter
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2009-00066 | REGISTRY | None | None |
| CDR0000434814 | None | None | None |
| URO 470 | OTHER | None | None |
| 6555 | OTHER | None | None |
| U01CA099177 | NIH | None | None |
| P30CA068485 | NIH | CTEP | httpsreporternihgovquickSearchP30CA068485 |