A Study Comparing Oral Picoplatin With Intravenous Picoplatin in Subjects With Solid Tumors

• MTD [ Time Frame: MTD ] [ Designated as safety issue: Yes ]
• Comparison of platinum levels excreted in urine from 0-8 and 8-24 hours after start of IV or oral drug [ Time Frame: PK ] [ Designated as safety issue: Yes ]

• Comparison of platinum levels excreted in urine from 0-8 and 8-24 hours after start of IV or oral drug.
• Comparison of platinum levels in plasma and plasma ultrafiltrate between IV and oral administration

Picoplatin is a new platinum-based chemotherapy drug that has been studied in a variety of cancers. Phase 1 and 2 studies have demonstrated that picoplatin may be effective in patients whose cancer returns or does not improve after treatment with chemotherapy. In these studies, picoplatin was administered intravenously. A capsule containing picoplatin has been formulated. This study will investigate the activity of the oral capsule in humans. Participants with advanced solid tumors will be enrolled.

The primary study design is a randomized, two-period crossover, open label study in which a single dose (Cycle 1) of picoplatin will be given either IV or by oral capsule, followed 4 weeks later by a single dose (Cycle 2) of picoplatin given either IV or by oral capsule (whichever route was not used in Cycle 1). Participants may continue to receive cycles of IV picoplatin every 3 weeks, beginning with Cycle 3, as part of a Continuation Study.

This study will determine the relative safety, bioavailability, pharmacokinetics, pharmacodynamics, and urinary excretion of picoplatin administered orally with reference to picoplatin administered intravenously.

• Bladder Cancer
• Breast Cancer
• Colorectal Cancer
• Gastrointestinal Neoplasm
• Head and Neck Cancer
• Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer

• Beale P, Judson I, O'Donnell A, Trigo J, Rees C, Raynaud F, Turner A, Simmons L, Etterley L. A Phase I clinical and pharmacological study of cis-diamminedichloro(2-methylpyridine) platinum II (AMD473). Br J Cancer. 2003 Apr 7;88(7):1128-34.
• Holford J, Raynaud F, Murrer BA, Grimaldi K, Hartley JA, Abrams M, Kelland LR. Chemical, biochemical and pharmacological activity of the novel sterically hindered platinum co-ordination complex, cis-[amminedichloro(2-methylpyridine)] platinum(II) (AMD473). Anticancer Drug Des. 1998 Jan;13(1):1-18.
• Raynaud FI, Boxall FE, Goddard PM, Valenti M, Jones M, Murrer BA, Abrams M, Kelland LR. cis-Amminedichloro(2-methylpyridine) platinum(II) (AMD473), a novel sterically hindered platinum complex: in vivo activity, toxicology, and pharmacokinetics in mice. Clin Cancer Res. 1997 Nov;3(11):2063-74.

Inclusion Criteria:

• Histological diagnosis of non-hematological malignancy.
• Patients for whom no standard therapy exists and for whom, in the opinion of the investigator, treatments with single agent picoplatin is appropriate.
• 18 years of age or older.
• ECOG performance status 0-2.
• Life expectancy of at least 12 weeks.

(Additional inclusion criteria apply.)

Exclusion Criteria:

• Symptomatic or uncontrolled brain metastases.
• Prior radiation involving ≥ 30% of the total bone marrow space.
• Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study.
• Gastrointestinal surgery that might interfere with absorption of orally administered drug.
• Active inflammatory bowel disease, gastritis, ulcers, gastrointestinal or rectal bleeding.
• Clinical evidence of pancreatic injury or active pancreatitis.
• Female subjects who are pregnant or breastfeeding.

(Additional exclusion criteria apply.)