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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Vadimezan™

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Univ. of Indiana School of Medicine/Simon Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center/ Clinical Trials Office
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine/Siteman Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy & Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients having a histologically-proven and radiologically-confirmed advanced or metastatic solid tumor.
2. WHO Performance Status of 0-2.
3. A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies.

4. 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:

1. Patients having CNS metastasis or evidence of leptomeningeal disease.

2. 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
3. History of neuroendocrine tumors (e.g. carcinoid tumor, pancreatic islet cell tumor).
4. Significant neurological or psychiatric disorder.
5. Smokers (use of cigarettes within the last 3 months).
6. Concomitant use of drugs that are associated with QTc interval prolongation or have a risk of causing torsade de pointes.
7. 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.
8. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: January 26, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (ESTIMATE): February 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 2, 2011
• Last Update Submitted That Met QC Criteria: August 31, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Oncology,; Phase I,; fluvoxamine,; ASA404,; CYP1A2,; drug drug interaction,; Novartis,; Antisoma
• Additional Relevant MeSH Terms: Antineoplastic Agents; Vadimezan
• Other Study ID Numbers: CASA404A2113