A Preoperative Biological Trial of Cetuximab, Dasatinib or the Combination in Colorectal Cancer Patients With Resectable Liver Metastases
- To evaluate the biological effects of cetuximab and/or dasatinib on epidermal growth
factor receptor (EGFR)and Src-signaling pathways in patients with colorectal cancer and
resectable liver metastases.
OUTLINE: This is a multicenter study. Patients are initially enrolled in cohort A. Once
cohort A is completed, additional patients are enrolled and randomized to treatment in
either cohorts B or C. If a significant biological effect is seen in cohorts B or C,
additional patients are enrolled in cohort D.
- Cohort A: Patients receive no systemic neoadjuvant therapy between enrollment and the
time of definitive surgical resection of liver metastases. Liver biopsies were
performed at surgery since this cohort received no systemic therapy.
- Cohort B: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on
day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical
resection of liver metastases will take place on day 15
- Cohort C: Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive
surgical resection of liver metastases will take place on day 15
- Cohort D: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on
day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg
orally once daily on days 1-14. Definitive surgical resection of liver metastases will
take place on day 15
Patients undergo tumor tissue (from initial liver tumor biopsies and liver resection
samples), serum, and peripheral blood mononuclear cell sample collection periodically for
biomarker analysis via immunohistochemistry (IHC).
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Patients With a Biologic Response
Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%).
on baseline and preoperatively on day of surgery (day 15)
Emily Chan, MD, Ph.D.
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Moffitt Cancer Center||Tampa, Florida 33612|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|