A Dose-escalation Pharmacokinetic Study of Intravenous ASA404 in Adult Advanced Cancer Patients With Impaired Renal Function and Patients With Normal Renal Function

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

The purpose of this study is to evaluate the safety and pharmacokinetics of ASA404 in patients with refractory or relapsed metastatic cancer with impaired renal function and with normal renal function. It is very possible that patients with renal impairment will show differences in renal excretion of parent ASA404 and its metabolites, warranting a study that leads to a better pharmacokinetic assesssment in this population.

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer
• Intervention / Treatment: Drug: ASA404, DMXAA or DXAA

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

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center, Hematology/Oncology Dept.
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Hematology /Oncology Associates
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Joseph Ford Cancer Center/Clinical Trials Office, Henry Ford Health System
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance

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 either refractory to standard chemotherapy;
• Patients whom chemotherapy with an investigaional agent in combination with docetaxel, or paclitaxel + carboplatin is appropriate;
• Creatinine clearance according to Cockcroft-Gault formula : Normal > 80 mL/min, Mild 50-80 mL/min, Moderate 30-<50 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;
• Body Mass Index (BMI) must be within the range of 18 and 30

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;
• Radiotherapy </- weeks prior to starting study drug;
• Major surgery </ 4 weeks prior to the start of study;
• 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, DMXAA or DXAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the pK of a single intravenous dose of ASA404 1200 and 1800 mg/m2 monotherapy in adult cancer patients with impaired renal function compared to matching patients with normal renal function	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the pharmacokinetics of a single i.v. dose of ASA 1200 and 1800 mg/m2 +chemotherapy (doctaxel or paclitaxel + carboplatin) in adult cancer patients with impaired renal function compared to matching patients with normal renal function	12 months
To assess the safety and tolerability of ASA404 in adult cancer patients with impaired renal function compared to matching patients with normal renal function	12 months
To assess the safety and tolerability of ASA404 1200 or 1800 mg/m2 in combination with chemotherapy (docetaxel or paclitaxel + carboplatin)
To evaluate ASA404 pharmacokinetic parameters including AUC (0-t last),), AUC (0-inf)), T ((½)), CL, V(Z), Cmax, and Tmax
To evaluate renal clearance (CLR) of ASA404.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Results for CASA404A2109 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: January 16, 2011
• First Submitted That Met QC Criteria: January 16, 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: tolerability; safety,; refractory,; Advanced or metastatic cancer,; core phase,; extension phase,; dose escalation,; standard chemotherapy,; doctaxel,; paclitaxel,; carboplatin,
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Kidney Diseases; Urologic Diseases; Neoplastic Processes; Neoplasm Metastasis; Renal Insufficiency; Antineoplastic Agents; Vadimezan
• Other Study ID Numbers: CASA404A2109; EudraCT 2009-017159-88 (Registry Identifier: EudraCT)