A Dose-escalation Pharmacokinetic Study of Intravenous ASA404 in Adult Advanced Cancer Patients With Impaired Renal Function and Patients With Normal Renal Function

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and pharmacokinetics of ASA404 in patients with refractory or relapsed metastatic cancer with impaired renal function and with normal renal function. It is very possible that patients with renal impairment will show differences in renal excretion of parent ASA404 and its metabolites, warranting a study that leads to a better pharmacokinetic assesssment in this population.

Official Title
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A Multi-center, Open-label, Dose-escalation Study to Assess the Pharmacokinetics of Intravenous ASA404 in Adult Advanced Cancer Patients With Impaired Renal Function and With Normal Renal Function

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Drug: ASA404, DMXAA or DXAA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients having histologically-proven solid tumors, who are either refractory to standard chemotherapy; Patients whom chemotherapy with an investigaional agent in combination with docetaxel, or paclitaxel + carboplatin is appropriate; Creatinine clearance according to Cockcroft-Gault formula : Normal > 80 mL/min, Mild 50-80 mL/min, Moderate 30-<50 mL/min; A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies; Potassium, calcium, magnesium and phosphorus values within the normal range; Body Mass Index (BMI) must be within the range of 18 and 30 Exclusion Criteria: Patients having CNS metastases, must have a CT or MRI of the brain performed to rule out CNS metastases; Patients with leptomeningeal disease metastases; Radiotherapy </- weeks prior to starting study drug; Major surgery </ 4 weeks prior to the start of study; Administration of CYP1A2 and CYP3A4/5 enzyme inducing or inhibiting drugs within 14 days prior to starting study drug; Other protocol-defined inclusion/exclusion criteria may 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASA404 + standard therpy<br> | Drug: ASA404, DMXAA or DXAA<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pK of a single intravenous dose of ASA404 1200 and 1800 mg/m2 monotherapy in adult cancer patients with impaired renal function compared to matching patients with normal renal function |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetics of a single i.v. dose of ASA 1200 and 1800 mg/m2 +chemotherapy (doctaxel or paclitaxel + carboplatin) in adult cancer patients with impaired renal function compared to matching patients with normal renal function |  | 12 months | 
| To assess the safety and tolerability of ASA404 in adult cancer patients with impaired renal function compared to matching patients with normal renal function |  | 12 months | 
| To assess the safety and tolerability of ASA404 1200 or 1800 mg/m2 in combination with chemotherapy (docetaxel or paclitaxel + carboplatin) |  |  | 
| To evaluate ASA404 pharmacokinetic parameters including AUC (0-t last),), AUC (0-inf)), T ((½)), CL, V(Z), Cmax, and Tmax |  |  | 
| To evaluate renal clearance (CLR) of ASA404. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extension phase,, Advanced or metastatic cancer,, refractory,, core phase,, dose escalation,, standard chemotherapy,, doctaxel,, paclitaxel,, carboplatin,, safety,, tolerability