Safety and Pharmacokinetics of ASA404 When Given Together With Fluvoxamine, a Selective Serotonin Receptor Reuptake Inhibitor and CYP1A2 Inhibitor

Study Overview
=================
Brief Summary
-----------------
This trial is designed to study the drug-drug interaction between ASA404 and fluvoxamine, an inhibitor of its metabolic pathway (CYP1A2). The study will consist of two phases. The purpose of the Core Phase is to study the drug drug interaction between fluvoxamine and ASA404. The purpose of the Extension Phase is to provide continued treatment for those patients that have not progressed during the Core Phase and to collect safety data on ASA404 when given in combination with paclitaxel, docetaxel or the paclitaxel plus carboplatin chemotherapy regimen.

Official Title
-----------------
A Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effects of Fluvoxamine on the Pharmacokinetics of ASA404 in Adult Patients With Solid Tumor Malignancies

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Drug: Vadimezan™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients having a histologically-proven and radiologically-confirmed advanced or metastatic solid tumor. WHO Performance Status of 0-2. A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies. Laboratory values within the ranges, as defined below: ANC ≥ 1.5 X 109 /L Platelets ≥ 100 X 109 /L Hemoglobin ≥ 10 g/dL Serum total bilirubin is within normal range Exclusion Criteria: Patients having CNS metastasis or evidence of leptomeningeal disease. Patients with any of the following: any clinical or electrocardiographic evidence of cadiac ischemia poorly controlled hypertension family history of unexplained sudden death long QT syndrome history of ventricular fibrillation or torsade de pointes congestive heart failure (NYHA class III or IV) myocardial infarction within 12 months of starting study treatment History of neuroendocrine tumors (e.g. carcinoid tumor, pancreatic islet cell tumor). Significant neurological or psychiatric disorder. Smokers (use of cigarettes within the last 3 months). Concomitant use of drugs that are associated with QTc interval prolongation or have a risk of causing torsade de pointes. Concomitant use of serotonin reuptake inhibitors (SSRIs), 5-hydroxytryptamine (5-HT) receptor agonists or selective serotonin / nor-epinephrine reuptake inhibitors (SNRIs) within 30 days prior to starting study treatment. Concomitant use of somatostain analogues (i.e. octreotide, lanreotide within 30 days prior to starting study treatment. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASA404 + Fluvoxamine<br>ASA404 + Fluvoxamine (Core Phase), ASA404 + either paclitaxel or docetaxel or paclitaxel plus carboplain chemotherapy combination (Extension Phase) | Drug: Vadimezan™<br> <br> * Other names: ASA404;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the effect of administration of fluvoxamine, a CYP1A2 inhibitor, after 2-cycles of ASA404, on the pharmacokinetics of ASA404 |  | approximately 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the effect of administration of fluvoxamine on the safety profile (incidence of AEs or SAEs generated) of ASA404 |  | 4 months | 
| assess the safety (incidence of AEs and SAEs) of ASA404 in combination with paclitaxel, doctaxel or the paclitaxel plus carboplatin chemotherapy regimen in patients with solid tumor malignancies |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ASA404,, Phase I,, Oncology,, CYP1A2,, fluvoxamine,, drug drug interaction,, Novartis,, Antisoma