An Open-label, Dose Escalation Study to Assess the Pharmacokinetics of of ASA404 in Adult Cancer Patients With Impaired Hepatic Function

A Multi-center, Open-label, Dose-escalation Study to Assess the Pharmacokinetics of ASA404 in Adult Cancer Patients With Impaired Hepatic Function and With Normal Hepatic Function

This study is designed to obtain pharmacokinetic data following a single-dose 20-minute i.v. administration of ASA404 (900, 1200, or 1800 mg/m2) in adult cancer patients with varying degrees of hepatic impairment. The study will be carried out in cancer volunteer patients (utilizing controls with normal hepatic function) who will be assigned to four hepatic impairment groups according to their pre-dose (Day-1) and total bilirubin level. The study will consist of two phases, a (Core Phase) that will evaluate the pharmacokinetics of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function, and compared to controls with normal hepatic function. The assessments will be done on the safety and tolerability of that single dose in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function. The Extension Phase will consist of assessing the safety and tolerability of ASA404 at the same three doses in combination with a sponsor-approved taxane-based regimen in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function.

Study Overview

• Status: Terminated
• Conditions: Histologically-proven and Radiologically-confirmed Solid Tumors
• Intervention / Treatment: Drug: ASA404

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 2104
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
• New Zealand
  • Auckland, New Zealand
    • Novarts Investigative Site
  • Wellington, 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:

• Patients having histologically-proven solid tumors, who are refractory to standard chemotherapy;
• Patients whom chemotherapy with an investigational agent in combination with docetaxel, or paclitaxel + carboplatin is appropriate;
• Age ≥ 18 years old
• Creatinine clearance according to Cockcroft-Gault formula ≥ 60 mL/min
• A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies;
• Potassium, calcium, magnesium and phosphorus values within the normal range Total bilirubin ≤ 6 X ULN

Exclusion Criteria:

• Patients having CNS metastases, must have a CT or MRI of the brain performed to rule out CNS metastases;
• Patients with leptomeningeal disease metastases;
• Major surgery </ 4 weeks prior to the start of study;
• Prior exposure to VDAs or other vascular targeting agents;
• Right bundle branch block (RBBB), complete left bundle branch block (LBBB);
• Administration of CYP1A2 and CYP3A4/5 enzyme inducing or inhibiting drugs within 14 days prior to starting study drug;

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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA404 + standard therpy	Drug: ASA404

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
(Core Phase)To evaluate the PK of a single intravenous dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function compared to matching patients with normal hepatic function	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function	18 months
(Extension Phase) assess the safety & tolerability of ASA404 either alone or in combination with a sponsor approved taxane-based regimen in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function	18 months
To assess the safety of the combined regimen on the frequency and severity of adverse events and the number of laboratory values worsening from baseline based on the CTCAE grade assessment.	18 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Results for CASA404A2105 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: January 17, 2011
• First Submitted That Met QC Criteria: January 17, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Actual): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: safety,; pharmacokinetics,; tolerability,; refractory,; hepatic impairment; Advanced or metastatic cancer,; core phase,; extension phase,; dose escalation,; standard chemotherapy,; doctaxel,; paclitaxel,; carboplatin,
• Additional Relevant MeSH Terms: Antineoplastic Agents; Vadimezan
• Other Study ID Numbers: CASA404A2105; EudraCT 2009-016471-30 (Registry Identifier: EudraCT)