BAY 43-9006 (Sorafenib) and Bevacizumab (Avastin) To Treat Solid Tumors
Status:
Completed
Trial end date:
2012-07-20
Target enrollment:
Participant gender:
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.