Ignite Creation Date:
2025-12-24 @ 7:33 PM
Ignite Modification Date:
2025-12-25 @ 5:15 PM
Study NCT ID:
NCT00378703
Status:
COMPLETED
Last Update Posted:
2018-11-14
First Post:
2006-09-19
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
The BeST Trial: A Randomized Phase II Study of VEGF, RAF Kinase, and mTOR Combination Targeted Therapy (CTT) With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma
Status:
COMPLETED
Status Verified Date:
2018-10
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 randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess progression-free survival on each arm of combination targeted therapy (CTT) compared to that of bevacizumab alone.
SECONDARY OBJECTIVES:
I. To assess the significance of changes in tumor size over early time points as a predictor of progression-free survival (PFS).
II. To quantify the number and percent of patients who have stable disease at 6 months of therapy (failure to progress) in each treatment arm of CTT in patients with metastatic renal cell carcinoma (RCC).
III. To evaluate the safety of each treatment arm of combination targeted therapy (CTT) in patients with metastatic RCC.
IV. To assess overall survival in each arm of the study. V. To assess the objective response rate in each treatment arm of CTT in patients with metastatic RCC.
VI. To assess pathology, angiogenesis histology and to assess activation status of mitogen activated protein (MAP) kinase and vascular endothelial growth factor receptor 2 (VEGFR2) pathways and relate to clinical outcome.
TERTIARY OBJECTIVES:
I. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib (sorafenib tosylate) including angiogenesis, monooxygenases polymorphisms and multi-drug resistance (MDR).
II. To relate changes in tumor perfusion and vascular permeability on serial dynamic contrast-enhanced magnetic resonance imaging (MRI) to clinical outcome and radiologic regression detected by other standard methods.
III. To assess the potential of dynamic contrast-enhanced (DCE)-MRI imaging as a biomarker for response to therapy and/or as a prognostic indicator of disease progression.
IV. To assess site readiness and ability in acquiring DCE-MRI data. V. To determine the relationship between tumor and blood biomarkers and clinical outcomes of patients treated with the combination of targeted agents.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM A: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.
ARM B: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.
ARM C: Patients receive bevacizumab as in Arm A and sorafenib tosylate orally (PO) twice daily (BID) on days 1-5, 8-12, 15-19, and 22-26.
ARM D: Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.
In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for 5 years.
I. To assess progression-free survival on each arm of combination targeted therapy (CTT) compared to that of bevacizumab alone.
SECONDARY OBJECTIVES:
I. To assess the significance of changes in tumor size over early time points as a predictor of progression-free survival (PFS).
II. To quantify the number and percent of patients who have stable disease at 6 months of therapy (failure to progress) in each treatment arm of CTT in patients with metastatic renal cell carcinoma (RCC).
III. To evaluate the safety of each treatment arm of combination targeted therapy (CTT) in patients with metastatic RCC.
IV. To assess overall survival in each arm of the study. V. To assess the objective response rate in each treatment arm of CTT in patients with metastatic RCC.
VI. To assess pathology, angiogenesis histology and to assess activation status of mitogen activated protein (MAP) kinase and vascular endothelial growth factor receptor 2 (VEGFR2) pathways and relate to clinical outcome.
TERTIARY OBJECTIVES:
I. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib (sorafenib tosylate) including angiogenesis, monooxygenases polymorphisms and multi-drug resistance (MDR).
II. To relate changes in tumor perfusion and vascular permeability on serial dynamic contrast-enhanced magnetic resonance imaging (MRI) to clinical outcome and radiologic regression detected by other standard methods.
III. To assess the potential of dynamic contrast-enhanced (DCE)-MRI imaging as a biomarker for response to therapy and/or as a prognostic indicator of disease progression.
IV. To assess site readiness and ability in acquiring DCE-MRI data. V. To determine the relationship between tumor and blood biomarkers and clinical outcomes of patients treated with the combination of targeted agents.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM A: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.
ARM B: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.
ARM C: Patients receive bevacizumab as in Arm A and sorafenib tosylate orally (PO) twice daily (BID) on days 1-5, 8-12, 15-19, and 22-26.
ARM D: Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.
In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for 5 years.
Study Oversight
Has Oversight DMC:
False
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2009-00533 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| ECOG-E2804 | None | None | View | |
| CDR0000499788 | None | None | View | |
| E2804 | OTHER | ECOG-ACRIN Cancer Research Group | View | |
| E2804 | OTHER | CTEP | View | |
| U10CA180820 | NIH | None | https://reporter.nih.gov/quic… | View |
| U10CA021115 | NIH | None | https://reporter.nih.gov/quic… | View |