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

Novartis

Status and phase

Terminated

Phase 1

Conditions

Histologically-proven and Radiologically-confirmed Solid Tumors

Treatments

Drug: ASA404

Study type

Interventional

Funder types

Industry

Identifiers

NCT01278849

EudraCT 2009-016471-30 (Registry Identifier)

CASA404A2105

Details and patient eligibility

About

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.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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