New Cancer Drug Gets First Trial in Humans
Phase 0 clinical trial of ABT-888 proves the approach, sets stage for Phase I clinical trials
THURSDAY, April 16 (HealthDay News) -- The first human trial of the experimental cancer drug poly (ADP-ribose) polymerase inhibitor ABT-888 has successfully demonstrated its inhibitory effect and paved the way for a phase I clinical trial, according to a report published online April 13 in the Journal of Clinical Oncology.
Shivaani Kummar, M.D., of the National Cancer Institute in Bethesda, Md., and colleagues recruited 13 patients with advanced cancer to participate in a phase 0 clinical trial of the experimental agent. The patients received the drug in a single oral dose of 10, 25 or 50 milligrams. Tumor biopsies and blood samples were taken before and after drug administration to evaluate drug action. The researchers used a novel statistical method to study pharmacodynamic results rather than toxicity.
With the 25 mg and 50 mg doses of ABT-888, the researchers observed significant (greater than 90 percent) inhibition of poly (ADP-ribose) in peripheral blood cells and tumor biopsies at three to six hours after drug administration. Bioavailability with oral administration was judged to be good and the drug was well tolerated.
"Within five months of study activation, we obtained pivotal biochemical and pharmacokinetic data that have guided the design of subsequent phase I trials of ABT-888 in combination with DNA-damaging agents. In addition to accelerating the development of ABT-888, the rapid conclusion of this trial demonstrates the feasibility of conducting proof-of-principle phase 0 trials as part of an alternative paradigm for early drug development in oncology," the authors write.
Several co-authors reported financial relationships with Abbott Laboratories and Genentech Inc., which are collaborating in the development of ABT-888.