An Open-label, Dose Escalation Study to Assess the Pharmacokinetics of of ASA404 in Adult Cancer Patients With Impaired Hepatic Function

Study Overview
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Brief Summary
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This study is designed to obtain pharmacokinetic data following a single-dose 20-minute i.v. administration of ASA404 (900, 1200, or 1800 mg/m2) in adult cancer patients with varying degrees of hepatic impairment. The study will be carried out in cancer volunteer patients (utilizing controls with normal hepatic function) who will be assigned to four hepatic impairment groups according to their pre-dose (Day-1) and total bilirubin level. The study will consist of two phases, a (Core Phase) that will evaluate the pharmacokinetics of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function, and compared to controls with normal hepatic function. The assessments will be done on the safety and tolerability of that single dose in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function. The Extension Phase will consist of assessing the safety and tolerability of ASA404 at the same three doses in combination with a sponsor-approved taxane-based regimen in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function.

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

Conditions
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Histologically-proven and Radiologically-confirmed Solid Tumors

Intervention / Treatment
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* Drug: ASA404


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients having histologically-proven solid tumors, who are refractory to standard chemotherapy; Patients whom chemotherapy with an investigational agent in combination with docetaxel, or paclitaxel + carboplatin is appropriate; Age ≥ 18 years old Creatinine clearance according to Cockcroft-Gault formula ≥ 60 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 Total bilirubin ≤ 6 X ULN 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; Major surgery </ 4 weeks prior to the start of study; Prior exposure to VDAs or other vascular targeting agents; Right bundle branch block (RBBB), complete left bundle branch block (LBBB); 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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Core Phase)To evaluate the PK of a single intravenous dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function compared to matching patients with normal hepatic function |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function |  | 18 months | 
| (Extension Phase) assess the safety & tolerability of ASA404 either alone or in combination with a sponsor approved taxane-based regimen in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function |  | 18 months | 
| To assess the safety of the combined regimen on the frequency and severity of adverse events and the number of laboratory values worsening from baseline based on the CTCAE grade assessment. |  | 18 months | 

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