Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 3:02 PM
Ignite Modification Date:
2025-12-24 @ 3:02 PM
NCT ID:
NCT00095459
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.
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.
Study:
NCT00095459
Study Brief:
Protocol Section:
NCT00095459