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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01278849
First received: January 17, 2011
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Histologically-proven and Radiologically-confirmed Solid Tumors
Drug: ASA404
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • (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 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • (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 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: January 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASA404 + standard therpy Drug: ASA404

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01278849

Locations
Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Milano, Italy, 2104
New Zealand
Novarts Investigative Site
Auckland, New Zealand
Novartis Investigative Site
Wellington, New Zealand
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Investigative Site
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01278849     History of Changes
Other Study ID Numbers: CASA404A2105, EudraCT 2009-016471-30
Study First Received: January 17, 2011
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Advanced or metastatic cancer,
refractory,
core phase,
extension phase,
dose escalation,
standard chemotherapy,
pharmacokinetics,
doctaxel,
paclitaxel,
carboplatin,
safety,
tolerability,
hepatic impairment

Additional relevant MeSH terms:
5,6-dimethylxanthenoneacetic acid
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014