Combining Sorafenib with standard cytotoxic fluoropyrimidine therapy for advanced colorectal cancer may provide clinical benefit when no other treatment remains.
The Raf/MEK/ERK pathway is an important mediator of responses to growth factors, and a strong inducer of genes involved in tumorigenesis, angiogenesis, apoptosis, and tumorigenesis in metastatic colorectal cancer (mCRC). Inhibition of this pathway has been previously proven to be highly clinically beneficial for patients with this disease. It has also been clearly demonstrated that the inhibition of VEGF, when coupled with cytotoxic therapy and/or continued beyond initial response, can improve clinical outcomes and survival in this same cohort of patients. Safety and pharmacokinetic data have already been established for this novel doublet oral chemotherapy. This study is intended to determine the activity of a combination of oral fluoropyrimidine plus sorafenib in an advanced mCRC patient population for whom limited treatment options remain.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days
UF Health Cancer Center
Gainesville, Florida, United States
Sorafenib Activity
Determine activity of sorafenib plus capecitabine on progression free survival (PFS) in patients with advanced colorectal cancer. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 2 years
Overall Survival
Evaluate overall survival after treatment.
Time frame: 5 years
Response Rate
This is the percentage of subjects that achieved either a complete response or a partial response per RECIST 1.1 criteria
Time frame: 3 months
Response Duration
This is the median response duration (median time from date of a complete or partial response to date of disease progression per RECIST 1.1 criteria) and includes only subjects that achieved either a complete or partial response to treatment per RECIST 1.1 criteria.
Time frame: up to 12 months
Toxicity (Percentage of Subjects That Experienced an Adverse Event)
Evaluate acute toxicity of treatment. The toxicity assessments were graded by the NCI CTCAE (Clinical Trial Common Adverse Event) grading system - a global standard for assessments of clinical and laboratory toxicities. All toxicities are scored 1(mild) through 5 (death related to the event) based upon well-defined and reproducible definitions.
Time frame: 12 months
Correlative Tissue Analysis
Exploratory tissue analysis in patients receiving sorafenib plus capecitabine
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Time frame: 6 months