Ignite Creation Date:
2024-05-05 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00095459
Status:
COMPLETED
Last Update Posted:
2019-12-17
First Post:
2004-11-04
Brief Title:
BAY 43-9006 Sorafenib and Bevacizumab Avastin To Treat Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Trial of BAY 43-9006 Sorafenib and Bevacizumab in Refractory Solid Tumors With Biologic and Proteomic Analysis
Status:
COMPLETED
Status Verified Date:
2014-04-23
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:
Background
BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro but it also inhibits p38 c-kit VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf
Bevacizumab is a humanized IgG1 monoclonal antibody MAb that binds all biologically active isoforms of human vascular endothelial growth factor VEGF or VEGF-A with high affinity kd 11nM
The most common adverse events associated with bevacizumab of any severity include asthenia pain headache hypertension diarrhea stomatitis constipation epistaxis dyspnea dermatitis and proteinuria
This Phase I trial is open to patients with all solid tumors
Objectives
Determine the safety and toxicity of the combination of BAY 43-9006 Sorafenib and bevacizumab
Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD at least in a pilot fashion if those changes are statistically significant
Eligibility
Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective
Patients must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy
ECOG performance status 0 or 1 and adequate organ and marrow function
Design
Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion
Cohort II will be randomized as to which agent they receive for cycle one Cycles 2 and beyond are treated using both agents
Tumor biopsies will be obtained from patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
DCE-MRI studies will be obtained on patients in Cohort II before treatment two weeks into monotherapy four weeks into monotherapy and two weeks into combinatorial therapy
FDG-PET studies will be obtained on patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2 and then every 4 weeks
Patients will be evaluated for response every 8 weeks using the RECIST criteria
Approximately 62 patients will be needed to achieve the objectives of the trial
BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro but it also inhibits p38 c-kit VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf
Bevacizumab is a humanized IgG1 monoclonal antibody MAb that binds all biologically active isoforms of human vascular endothelial growth factor VEGF or VEGF-A with high affinity kd 11nM
The most common adverse events associated with bevacizumab of any severity include asthenia pain headache hypertension diarrhea stomatitis constipation epistaxis dyspnea dermatitis and proteinuria
This Phase I trial is open to patients with all solid tumors
Objectives
Determine the safety and toxicity of the combination of BAY 43-9006 Sorafenib and bevacizumab
Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD at least in a pilot fashion if those changes are statistically significant
Eligibility
Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective
Patients must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy
ECOG performance status 0 or 1 and adequate organ and marrow function
Design
Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion
Cohort II will be randomized as to which agent they receive for cycle one Cycles 2 and beyond are treated using both agents
Tumor biopsies will be obtained from patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
DCE-MRI studies will be obtained on patients in Cohort II before treatment two weeks into monotherapy four weeks into monotherapy and two weeks into combinatorial therapy
FDG-PET studies will be obtained on patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2 and then every 4 weeks
Patients will be evaluated for response every 8 weeks using the RECIST criteria
Approximately 62 patients will be needed to achieve the objectives of the trial
Detailed Description:
Background
BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro but it also inhibits p38 c-kit VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf
Bevacizumab is a humanized IgG1 monoclonal antibody MAb that binds all biologically active isoforms of human vascular endothelial growth factor VEGF or VEGF-A with high affinity kd 11nM
The most common adverse events associated with bevacizumab of any severity include asthenia pain headache hypertension diarrhea stomatitis constipation epistaxis dyspnea dermatitis and proteinuria
This Phase I trial is open to patients with all solid tumors
Objectives
Determine the safety and toxicity of the combination of BAY 43-9006 Sorafenib and bevacizumab
Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD at least in a pilot fashion if those changes are statistically significant
Eligibility
Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective
Patients must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy
ECOG performance status 0 or 1 and adequate organ and marrow function
Design
Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion
Cohort II will be randomized as to which agent they receive for cycle one Cycles 2 and beyond are treated using both agents
Tumor biopsies will be obtained from patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
DCE-MRI studies will be obtained on patients in Cohort II before treatment two weeks into monotherapy four weeks into monotherapy and two weeks into combinatorial therapy
FDG-PET studies will be obtained on patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2 and then every 4 weeks
Patients will be evaluated for response every 8 weeks using the RECIST criteria
Approximately 62 patients will be needed to achieve the objectives of the trial
BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro but it also inhibits p38 c-kit VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf
Bevacizumab is a humanized IgG1 monoclonal antibody MAb that binds all biologically active isoforms of human vascular endothelial growth factor VEGF or VEGF-A with high affinity kd 11nM
The most common adverse events associated with bevacizumab of any severity include asthenia pain headache hypertension diarrhea stomatitis constipation epistaxis dyspnea dermatitis and proteinuria
This Phase I trial is open to patients with all solid tumors
Objectives
Determine the safety and toxicity of the combination of BAY 43-9006 Sorafenib and bevacizumab
Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD at least in a pilot fashion if those changes are statistically significant
Eligibility
Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective
Patients must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy
ECOG performance status 0 or 1 and adequate organ and marrow function
Design
Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion
Cohort II will be randomized as to which agent they receive for cycle one Cycles 2 and beyond are treated using both agents
Tumor biopsies will be obtained from patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
DCE-MRI studies will be obtained on patients in Cohort II before treatment two weeks into monotherapy four weeks into monotherapy and two weeks into combinatorial therapy
FDG-PET studies will be obtained on patients in Cohort II before treatment two weeks into mono-therapy and two weeks into combinatorial therapy
Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2 and then every 4 weeks
Patients will be evaluated for response every 8 weeks using the RECIST criteria
Approximately 62 patients will be needed to achieve the objectives of the trial
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 |
|---|---|---|---|
| 05-C-0022 | None | None | None |