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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT01299415

Collaborator

(none)

Enrollment

Locations

Arm

4.3

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Vadimezan™	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ASA404 + Fluvoxamine ASA404 + Fluvoxamine (Core Phase), ASA404 + either paclitaxel or docetaxel or paclitaxel plus carboplain chemotherapy combination (Extension Phase)	Drug: Vadimezan™ Other Names: ASA404

Arm

Intervention/Treatment

Experimental: ASA404 + Fluvoxamine

ASA404 + Fluvoxamine (Core Phase), ASA404 + either paclitaxel or docetaxel or paclitaxel plus carboplain chemotherapy combination (Extension Phase)

Drug: Vadimezan™

Other Names:

ASA404

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. of Indiana School of Medicine/Simon Cancer Center	Indianapolis	Indiana	United States	46202
2	Masonic Cancer Center/ Clinical Trials Office	Minneapolis	Minnesota	United States	55455
3	Washington University School of Medicine/Siteman Cancer Center	St. Louis	Missouri	United States	63110
4	Cancer Therapy & Research Center	San Antonio	Texas	United States	78229