A Dose-Ranging, Phase II, Open Label Study of ATN 161 in Advanced Renal Cell Cancer
Angiogenesis, defined as the growth of new blood vessels from pre-existing vessels, is a
requirement for the growth of nearly all tumors. Clear cell renal cell carcinoma (CCRCC) is
a malignancy characterized by abundant vascularization and a high degree of resistance to
chemotherapy which makes antiangiogenic therapy an intriguing concept for treatment. This
concept has been established by the initial successes observed in recent studies of
antiangiogenic therapies for CCRCC. ATN-161 is an attractive candidate for investigation as
a therapeutic agent in CCRCC because it binds to several fully activated integrins, which
are essential downstream components in the angiogenic signaling cascade.
Functional imaging using dceMRI has been demonstrated as an effective way to show effects on
the vasculature across different tumors, including CCRCC. Preclinical experiments have
shown that ATN-161 affects tumor perfusion in tumor bearing mice. Therefore, use of imaging
in this study is expected to be an effective method for evaluating the antiangiogenic
response to ATN-161.
Patients will be administered ATN-161 three times weekly by short (10 minute) IV infusion at
1 of 3 dose levels (20, 100, and 600 mg). Patients will be treated until progression of
disease, unacceptable drug toxicity, or withdrawal of consent occurs.
Functional imaging (dceMRI) will be performed within 1 week prior to first treatment, again
during the second week of treatment, and finally during the fourth week of treatment.
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Reduction in tumor blood flow and permeability of vessels
United States: Food and Drug Administration
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|The Cleveland Clinic Foundation||Cleveland, Ohio|
|University of California Irvine, Chao Family Comprehensive Cancer Center||Irvine, California 92868|
|University of California San Francisco Comprehensive Cancer Center||San Francisco, California 94115|