An Open_Label, Single-Arm,Dose-Escalation Phase 1 Study of G-202 in Patients With Advanced Solid Tumors
Pro-drug chemotherapy is an approach to cancer treatment that is being investigated as a
means to achieve higher concentrations of cytotoxic or biologically active agents at a tumor
location while avoiding systemic toxicity. With pro-drug chemotherapy, a relatively
non-toxic form of a cytotoxin, the pro-drug, is converted into the active cytotoxic agent at
the tumor site or other specific location. G-202 is a thapsigargin pro-drug; it consists of
a cytotoxic analog of thapsigargin coupled to a masking peptide which inhibits its biologic
activity until proteolytic cleavage at the tumor site. Thapsigargin is a natural product
with profound effects on cell viability. Thapsigargin is a non-cell-type specific toxin
with documented ability to kill a broad spectrum of cancer cell lines as well as normal
endothelial cells, fibroblasts and osteoblasts. It induces a rapid and pronounced increase
in the concentration of cytosolic calcium, due to blockade of the Sarcoplasmic/Endoplasmic
Reticulum Calcium ATPase (SERCA) pump to which it binds with high affinity. The increase in
cytosolic calcium leads to induction of apoptosis and ensuing cell death.
The anti-tumor effect of G-202 in humans with advanced solid tumors is not yet known.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the MTD and DLT(s) of G-202 administered by intravenous infusion daily for 3 consecutive days on a 28-day cycle in patients with advanced solid tumors.
George Wilding, M.D
University of Wisconsin, Madison
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|University of Texas, Health Science Center,Cancer Therapy and Research Center||San Antonio, Texas 78229|
|University of Wisconsin Paul P Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792|