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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01299415
• Other study ID #: CASA404A2113
• Status: Terminated
• Phase: Phase 1
• First received: January 26, 2011
• Last updated: August 31, 2011
• Start date: August 2009

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Vadimezan™

Locations

Country	Name	City	State
United States	Univ. of Indiana School of Medicine/Simon Cancer Center	Indianapolis	Indiana
United States	Masonic Cancer Center/ Clinical Trials Office	Minneapolis	Minnesota
United States	Cancer Therapy & Research Center	San Antonio	Texas
United States	Washington University School of Medicine/Siteman Cancer Center	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	evaluate the effect of administration of fluvoxamine, a CYP1A2 inhibitor, after 2-cycles of ASA404, on the pharmacokinetics of ASA404		approximately 2 months	No
Secondary	evaluate the effect of administration of fluvoxamine on the safety profile (incidence of AEs or SAEs generated) of ASA404		4 months	No
Secondary	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	No