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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Picoplatin


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>two-period crossover, open label study in which a single dose (Cycle 1) of picoplatin will be given either IV or PO, followed 4 weeks later by a single dose (Cycle 2) of picoplatin given by the route not used for Cycle 1. Subjects subsequently may continue to receive IV picoplatin commencing with Cycle 3 in a Continuation Study. | Drug: Picoplatin<br>* The IV dose will be 120 mg/m2. Three oral dose levels will be studied sequentially (6 subjects per dose level) in the absence of dose limiting toxicity 200 mg, 300 mg, or 400 mg total dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD |  | MTD | 
| Comparison of platinum levels excreted in urine from 0-8 and 8-24 hours after start of IV or oral drug |  | PK | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Picoplatin, tumor, cancer, sarcoma, neoplasm, advanced, platinum, chemotherapy, Solid Tumor