Safety Study of Increasing Doses of Combretasatin A1 Diphosphate (OXi4503) as Monotherapy in Subjects With Hepatic Tumor Burden (OXi4503)

A Multicenter, Open-label Phase 1b/2 Study to Assess the Safety and Clinical Activity of Intravenous Combretastatin A1 Diphosphate (OXi4503) as Monotherapy in Subjects With Primary or Secondary Hepatic Tumor Burden

The purpose of this study is to determine the safety and tolerability of OXi4503 in subjects with relapsed or refractory carcinomas with hepatic tumor burden.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis
• Intervention / Treatment: Drug: Combretastatin A1 Diphosphate (OXi4503)

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • OXiGENE Investigational Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • OXiGENE Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • OXiGENE Investigational Site
  • Victoria
    • Bentleigh, Victoria, Australia, 3165
      • OXiGENE Investigational 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:

1. Histologically or cytologically confirmed carcinoma. Tumor must be relapsed or refractory to standard therapies, or have no acceptable standard therapy.
2. Measurable disease by RECIST criteria.
3. Subjects must be at least 28 days from other investigational therapy and at least 2 weeks after chemotherapy or radiation therapy.
4. Age 18 years or older.
5. Eastern Cooperative Oncology Group (ECOG) Performance Score of less than 1.
6. Life expectancy of greater than 12 weeks.
7. Hemoglobin greater than 10 g/dL.
8. Adequate hepatic function.
9. Adequate renal function.
10. Adequate bone marrow reserve.
11. Able to maintain potassium, calcium and magnesium levels within normal ranges.
12. Must be able to provide written informed consent.
13. All women of childbearing potential (WOCBP) must have a negative serum pregnancy test.
14. WOCBP and fertile men and their partners must agree to use an effective form of contraception during the study and for 90 days after the last dose of study medication.

Exclusion Criteria:

1. Uncontrolled CNS metastases.
2. No other active malignancies.
3. Poorly controlled hypertension.
4. Recent history of serious cardiovascular conditions.
5. Recent history of CVA, TIA, or intermittent claudication.
6. Current anticoagulation therapy.
7. History of cardiac arrhythmias.
8. Abnormal ECG findings.
9. Subjects who require concomitant medications which cause QTc prolongation.
10. Major surgery within 30 days of treatment, or minor surgery within 7 days of treatment.
11. Uncontrolled, clinically significant active infection.
12. Subjects who are pregnant or lactating.
13. Subjects with any other intercurrent medical condition.
14. Subjects with a history of solid organ transplant or bone marrow transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combretastatin A1 Diphosphate	Drug: Combretastatin A1 Diphosphate (OXi4503); OXi4503 administered IV on Days 1, 8, and 15 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of OXi4503 in subjects with relapsed or refractory carcinomas with hepatic tumor burden.	6 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine progression-free survival (PFS).	6 Months

Collaborators and Investigators

• Sponsor: Mateon Therapeutics
• Investigators: Principal Investigator: Michael Brown, MD, Royal Adelaide Hospital; Principal Investigator: Jason Lickliter, MD, Monash Medical Centre; Principal Investigator: Paul Mainwaring, MD, Mater Adult Hospital; Principal Investigator: Michael Millward, MD, Sir Charles Gairdner Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: August 14, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Estimate): August 23, 2011
• Last Update Submitted That Met QC Criteria: August 22, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: carcinoma; Vascular Disrupting Agent; liver cancer; hepatic carcinoma; VDA; hepatic cancer; hepatic tumor burden; liver carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Combretastatin
• Other Study ID Numbers: OXC101-100