Clinical trial NCT00465725: A Study Comparing Oral Picoplatin With Intravenous Picoplatin in Subjects With Solid Tumors
Official title: A Randomized Crossover Oral Bioavailability Study Comparing the Pharmacokinetics and Pharmacodynamics of Picoplatin Administered Orally With Picoplatin Administered Intravenously in Subjects With Advanced Non-Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bladder Cancer
Breast Cancer
Colorectal Cancer
Gastrointestinal Neoplasm
Head and Neck Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Keywords: Picoplatin
tumor
cancer
sarcoma
neoplasm
advanced
platinum
chemotherapy
Solid Tumor
Lead sponsor: Poniard Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-04-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.)

Primary outcomes:
measure: MTD
timeFrame: MTD
measure: Comparison of platinum levels excreted in urine from 0-8 and 8-24 hours after start of IV or oral drug
timeFrame: PK
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
Study officials:
affiliation: Poniard Pharmaceuticals
name: Robert Earhart, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1038/sj.bjc.6600854.
citation: 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.
citation: 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.