A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors
RB94, a tumor suppressor gene, is a modified form of the retinoblastoma gene, RB110. RB94
has shown enhanced tumor suppressor and tumor cell killing activity compared to RB110 in all
tumor cell types studied to date, including bladder cancer cell lines. Moreover, RB94 has
shown no toxicity to any normal human cells tested.
SGT-94,the agent being tested, is a systemically administered complex composed of the RB94
gene (plasmid DNA)encapsulated in a liposome that is targeted to tumor cells by means of an
anti-transferrin receptor single chain antibody fragment (TfRscFv)attached to the outside of
the liposome. Pre-clinical in vivo efficacy studies have indicated that SGT-94, when
systemically administered, preferentially targets tumor cells and efficiently transfects
them. This results in cancer cell death via mechanisms that are unique for RB94 and also
increases the tumor's response to conventional radiation and chemotherapy.
This Phase I study is designed to evaluate the safety of SGT-94 and to establish a
practically attainable and/or tolerable dose of this anti-cancer agent for use in further
clinical trials. Additionally, evidence of RB94 expression within tumor tissue after
systemic administration of SGT-94 will be sought, and clinically observable anti-cancer
effects in patients will be documented. Enrollment will be targeted to individuals with "RB
negative" tumors, i.e. tumors in which there is no staining for RB protein by
immunohistochemistry (IHC). Preference will be given to patients with tumors in a location
amenable to biopsy following treatment with SGT-94. This would include the prostate,
bladder, superficial lymph nodes and any mass suitable for fine needle aspiration under CT
or ultrasound guidance, or any lesion reachable by endoscopy.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Severity of Adverse Events
The severity of adverse experiences in each patient will be determined based upon changes in the results of clinical laboratory tests and physical examnations. These findings will be used to determine the safety and tolerability of increasing doses of SGT-94.
4 weeks each patient
Randall E Millikan, M.D., Ph.D.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|University of Texas, M.D. Anderson Cancer Center||Houston, Texas 77030|