Phase I Safety Study of DMXAA in Refractory Tumors

NCT00856336 | Completed Phase 1 DMC

• 1 other identifier: DART
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a phase I study aimed at identifying safe doses of DMXAA (now known as ASA404) to be used in future combination studies with chemotherapy.

Conditions

Refractory Tumors

Outcome Measures

Primary Outcomes (1)

• To identify a range of doses for DMXAA where there was either no effect or an acceptably small effect on QTc

Secondary Outcomes (6)

• To investigate and describe the relationship between QTc prolongation, plasma levels of DMXAA and time from start of infusion.

• To further investigate the safety profile of DMXAA

• To further investigate the pharmacokinetic behaviour of DMXAA

• To further characterise the ophthalmic effects of DMXAA

• To document anti-tumour activity and/or clinical signs of efficacy in patients

Interventions

DMXAA DRUG

DMXAA, given intravenously over 20 minutes. Patients were to each undergo six doses of treatment at weekly intervals, receiving each of six doses (300, 600, 1200, 1800, 2400 and 3000 mg/m2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of cancer, by histopathology or cytology, which was not amenable to any standard therapy or was refractory to conventional therapy
• Age ≥ 18 years
• Life expectancy of at least 12 weeks
• WHO performance status of 0-2
• Hematological and biochemical indices at the start of treatment:
• Hemoglobin at least 9 g/dl
• Leukocyte count at least 3.0 x 109/l
• Neutrophils at least 1.5 x 109/l
• Platelets at least 100 x 109/l
• Serum Creatinine not higher than140 μmol/l
• Liver function tests (ALT, AST, ALK PHOS) no higher than thrice the upper limit of the reference range, if no demonstrable liver metastases or no more than 5 x upper limit of the normal range in the presence of liver or bone metastases
• Absolute QTc interval values of less than 470 ms in females and less than 450 ms in males as assessed by the Investigator
• Presence of a lesion which was amenable to dynamic MRI
• Written informed consent and the ability of the patient to co-operate with treatment and follow up

You may not qualify if:

• Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks prior to treatment
• Pregnant or lactating women were excluded
• Patients who were poor medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection
• Current malignancies at other sites
• Significant history of recreational drug abuse
• Glucocorticosteroids in doses exceeding those required for physiological replacement within the previous 2 weeks
• Skin lesions that may prevent long-term ECG acquisition
• Body mass index above 30 kg/m2
• Patients who were taking certain medications
• Patients with clinical evidence of brain metastases
• Patients with certain cardiac conditions
• Advancing or unstable ischemic heart disease
• Pacing devices and/or implantable cardiovertor-defibrillator
• Significant cardiovascular disease or any unstable cardiovascular disease
• Non-sustained or sustained atrial and/or ventricular tachyarrhythmias

Sponsors & Collaborators

• Antisoma Research: lead

Related Publications (2)

• McKeage MJ, Fong P, Jeffery M, Baguley BC, Kestell P, Ravic M, Jameson MB. 5,6-Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent. Clin Cancer Res. 2006 Mar 15;12(6):1776-84. doi: 10.1158/1078-0432.CCR-05-1939.

  PMID: 16551862 RESULT

• Jameson MB, Sharp DM, Sissingh JI, Hogg CR, Thompson PI, McKeage MJ, Jeffery M, Waller S, Acton G, Green C, Baguley BC. Transient retinal effects of 5,6-dimethylxanthenone-4-acetic acid (DMXAA, ASA404), an antitumor vascular-disrupting agent in phase I clinical trials. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2553-9. doi: 10.1167/iovs.08-2068. Epub 2009 Apr 22.

  PMID: 19387077 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

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Study Officials

• Mark McKeage

  The University of Auckland

  PRINCIPAL INVESTIGATOR

• Michael Jameson

  Waikato Hospital

  PRINCIPAL INVESTIGATOR

• Mark Jeffery

  Christchurch Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 4, 2009
• First Posted: March 5, 2009
• Study Start: May 1, 2003
• Primary Completion: January 1, 2004
• Study Completion: January 1, 2004
• Last Updated: March 5, 2009

Record last verified: 2009-03