A Single Center Study to Characterize the Absorption, Distribution, Metabolism and Excretion (ADME) of ASA404 After a Single Infusion in Patients With Solid Tumors

An Open-label Single Center Study to Characterize the Absorption, Distribution, Metabolism, and Excretion (ADME) of ASA404 After a Single Intravenous Infusion of 3000 mg [14C]ASA404 in Patients With Advanced Solid Tumor Malignancies

This study is designed to characterize the absorption, distribution, metabolism and excretion (ADME) of ASA404 following a single intravenous administration of 3000 mg (approximately 1800 mg/m2) ASA404 containing 60 µCi of 14C over a period of 20 minutes in patients with advanced solid tumors. Metabolic pathways, route (s) of elimination, distribution characteristics in plasma and blood, and exposure characterization in plasma and blood, and exposure characterization of the parent drug and metabolites will be obtained from the study.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ASA404

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Grafton, Auckland, New Zealand
    • Novartis Investigative Site

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:

• Histologically proven diagnosis of advanced or metastatic solid tumors for whom either refractory to standard therapy exists, or for whom treatment with an investigational agent alone or in combination with docetaxel, paclitaxel, carboplatin, or paclitaxel plus carboplatin is appropriate;
• ANC≥ 1.5 x 109/L;
• Hgb ≥ 9.0 g/L;
• PLT ≥ 100,000/mm3;
• Total bilirubin ≤ 1.5;
• Willing and able to remain in the clinic for at least 4 days

Exclusion Criteria:

• Patients with CNS and/or leptomeningeal disease metastases allowed on the study unless asymptomatic and not requiring corticosteroid therapy. Patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for study participation. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed;
• Patients unable to undergo intravenous infusion;
• Patients with a Baseline 12-lead EGC QTc of >450 msec;
• Radiotherapy in less than two (2) weeks prior to study entry;
• A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA404	Drug: ASA404; (5,6-dimethylxanthenone-4-acetic acid) DMXAA or DXAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
characterize the pharmacokinetic profiles of ASA404 and any potential metabolite(s) in plasma and pharmacokinetic profiles of the total radioactivity in blood and plasma after a single intravenous infusion of 3000 mg [14C] ASA404 (60 µCi)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
determine the rate and routes of excretion of ASA404 (60 µCi)	12 months
identify metabolite(s) structures(s) and quantify the metabolites of ASA404 in plasma, urine, and feces in order to elucidate the biotransformation pathways and determine the essential clearance mechanisms of ASA404	12 months
collect safety data (including electrocardiograms) for ASA404	12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Investigative

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimate): February 18, 2011

Study Record Updates

• Last Update Posted (Actual): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: tolerability; safety; paclitaxel; carboplatin; refractory; docetaxel; dose escalation; core phase; extension phase; Advanced or metastatic cancer; standard chemotherapy
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Vadimezan
• Other Study ID Numbers: CASA404A2108