A phase IB trial of intravenous INO-1001 plus oral temozolomide in subjects with unresectable stage-III or IV melanoma.

Abstract	INO-1001 is a PARP-1 inhibitor that interrupts the repair process of N-methylpurines generated by temozolomide. We evaluated the pharmacokinetics of INO-1001 and determined its safety when used with temozolomide at 200 mg/m(2)/day x 5 days every 4 weeks. We enrolled 12 adult patients, in cohorts of 3-6 patients, into the study. INO-1001 at doses of 100, 200 and 400 mg was given intravenous for 1 hr q 12 hr for 10 doses. INO-1001 had a moderate clearance, volume of distribution and a relatively short terminal half-life. Myelosuppression and elevation of liver transaminases were dose-limiting toxicities (DLTs) of INO-1001 at 400 mg.
Authors	Agop Y Bedikian, Nicholas E Papadopoulos, Kevin B Kim, Wen-Jen Hwu, Jade Homsi, Michelle R Glass, Suzanne Cain, Patrick Rudewicz, Laurent Vernillet, Patrick Hwu
Journal	Cancer investigation (Cancer Invest) Vol. 27 Issue 7 Pg. 756-63 (Aug 2009) ISSN: 1532-4192 [Electronic] England
PMID	19440934 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	INO 1001 Indoles Neoplasm Proteins Poly(ADP-ribose) Polymerase Inhibitors Dacarbazine PARP1 protein, human Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Temozolomide
Topics	Administration, Oral Aged Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use) Bone Marrow Diseases (chemically induced) Chemical and Drug Induced Liver Injury (diagnosis, etiology) DNA Mismatch Repair Dacarbazine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, pharmacology) Drug Administration Schedule Female Humans Indoles (administration & dosage, adverse effects, pharmacokinetics, pharmacology) Infusions, Intravenous Male Melanoma (drug therapy, secondary) Middle Aged Neoplasm Proteins (antagonists & inhibitors, physiology) Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases (physiology) Temozolomide

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