Ignite Creation Date:
2025-12-24 @ 3:02 PM
Ignite Modification Date:
2026-04-09 @ 7:54 PM
Study NCT ID:
NCT00095459
Status:
COMPLETED
Last Update Posted:
2019-12-17
First Post:
2004-11-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
BAY 43-9006 (Sorafenib) and Bevacizumab (Avastin) To Treat Solid Tumors
Sponsor:
National Cancer Institute (NCI)
Organization:
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 (k(d)= 1.1nM)
* 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 (k(d)= 1.1nM)
* 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 (k(d)= 1.1nM)
* 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 (k(d)= 1.1nM)
* 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:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 05-C-0022 | None | None | View |