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The purpose of this study is to evaluate the potential inhibitory effects of ASA404 on CYP1A2, CYP2C9, CYP3A4 and CYP2C19 mediated metabolism on the respective probe drugs caffeine, diclofenac, simvastatin, and omeprazole, respectively. This will be accomplished by the simultaneous administration of four substrates as part of a cocktail in order to characterize the potential for in-vivo drug-drug interactions. This cocktail approach has been proposed per FDA guidance as a screening tool for potential in-vivo drug-drug interactions Compared to the individual administration of specific probes in multiple studies, simultaneous administration of multiple in-vivo probes of drug-metabolizing enzymes offer several distinct advantages such as minimizing the confounding influence of inter-individual and intra-individual variability over time. Substrates for the CYP enzymes were chosen based on the FDA guidance recommendations taking into account that 1. The substrates are specific for the individual CYP enzymes, 2. There are no interactions among these substrates; and 3. The study will be conducted in a sufficient number of subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ASA 404 + standard chemotherapy | Experimental | ASA 404 in combination with in combination with standard chemotherapy (paclitaxel + carboplatin or docetaxel) and a cocktail of caffeine, diclofenac, simvastatin and omeprazole |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ASA404, DMXAA, DXAA | Drug | ASA404 (5,6-dimethylxantheone-4-acetic acid) DMXAA or DXAA |
|
| Measure | Description | Time Frame |
|---|---|---|
| evaluate the effects of ASA404 on the pharmacokinetics of a cocktail of simvastatin, caffeine, omeprazole, and diclofenac in patients with advanced malignancies. | 12 months | |
| evaluate the effects of ASA404 combined with either paclitaxel + carboplatin or docetaxel on the pharmacokinetics of a cocktail of simvastatin, caffeine, omeprazole, and diclofenac in patients with advanced malignancies. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic parameters of caffeine, diclofenca, simvastatin, and omeprazole, including AUC (0-tlast), AUC (0-inf), t½,CL/F, Vz/F, Cmax, and tmax. | 12 months | |
| Pharmacokinetic parameters of ASA404 including AUC (0-tlast), Cmax, and Tmax | 4 Months |
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Inclusion Criteria:
Histologically-proven and radiologically-confirmed diagnosis of advanced or metastatic solid tumors for whom treatment with an investigational agent alone or in combination with docetaxel or placlitaxel +carboplatin is appropriate;
Exclusion Criteria:
If patient will be treated with paclitaxel:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Science Center at Houston | Houston | Texas | 77030 | United States | ||
| University of Wisconsin & Paul P. Carbone Comprehensive Cancer Center |
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| assessment of safety based mainly on the frequency and severity of adverse events and the number of laboratory values worsening from baseline based on the CTCAE grade. | Other safety data (e.g. vital signs, electrocardiograms, and ophthalmic assessments) will be considered as appropriate. | 4 months |
| assess the safety and tolerability of ASA404 | 4 months |
| Madison |
| Wisconsin |
| 53792 |
| United States |
| ID | Term |
|---|---|
| C066668 | vadimezan |
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