Phase I Safety Study of DMXAA in Refractory Tumors (DART)

This study has been completed.
Sponsor:
Information provided by:
Antisoma Research
ClinicalTrials.gov Identifier:
NCT00856336
First received: March 4, 2009
Last updated: NA
Last verified: March 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Refractory Tumors
Drug: DMXAA
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA) in the Treatment of Refractory Tumors: A Phase I Multicentre Doubleblind Randomized Six-Way Intrapatient Dose-Ranging Crossover Safety Study.

Resource links provided by NLM:


Further study details as provided by Antisoma Research:

Primary Outcome Measures:
  • To identify a range of doses for DMXAA where there was either no effect or an acceptably small effect on QTc [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate and describe the relationship between QTc prolongation, plasma levels of DMXAA and time from start of infusion. [ Designated as safety issue: Yes ]
  • To further investigate the safety profile of DMXAA [ Designated as safety issue: Yes ]
  • To further investigate the pharmacokinetic behaviour of DMXAA [ Designated as safety issue: No ]
  • To further characterise the ophthalmic effects of DMXAA [ Designated as safety issue: Yes ]
  • To document anti-tumour activity and/or clinical signs of efficacy in patients [ Designated as safety issue: No ]
  • To assess the effects of DMXAA on tumour blood flow using dynamic MRI [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: May 2003
Study Completion Date: January 2004
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: DMXAA
    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)
Detailed Description:

This was a multi-centre randomized, double blind study to further characterize the effect of DMXAA on QTc interval, ophthalmic safety and pharmacodynamic effects on tumour blood flow.

Patients with refractory tumors were to each undergo six doses of treatment at weekly intervals, receiving each of six doses of DMXAA (300, 600, 1200, 1800, 2400 and 3000 mg/m2)

  Eligibility

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

Inclusion Criteria:

  1. Evidence of cancer, by histopathology or cytology, which was not amenable to any standard therapy or was refractory to conventional therapy
  2. Age ≥ 18 years
  3. Life expectancy of at least 12 weeks
  4. WHO performance status of 0-2
  5. Hematological and biochemical indices at the start of treatment:

    1. Hemoglobin at least 9 g/dl
    2. Leukocyte count at least 3.0 x 109/l
    3. Neutrophils at least 1.5 x 109/l
    4. Platelets at least 100 x 109/l
    5. Serum Creatinine not higher than140 μmol/l
    6. 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
    7. Absolute QTc interval values of less than 470 ms in females and less than 450 ms in males as assessed by the Investigator
  6. Presence of a lesion which was amenable to dynamic MRI
  7. Written informed consent and the ability of the patient to co-operate with treatment and follow up

Exclusion Criteria:

  1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks prior to treatment
  2. Pregnant or lactating women were excluded
  3. Patients who were poor medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection
  4. Current malignancies at other sites
  5. Significant history of recreational drug abuse
  6. Glucocorticosteroids in doses exceeding those required for physiological replacement within the previous 2 weeks
  7. Skin lesions that may prevent long-term ECG acquisition
  8. Body mass index above 30 kg/m2
  9. Patients who were taking certain medications
  10. Patients with clinical evidence of brain metastases
  11. Patients with certain cardiac conditions

    1. Advancing or unstable ischemic heart disease
    2. Pacing devices and/or implantable cardiovertor-defibrillator
    3. Significant cardiovascular disease or any unstable cardiovascular disease
    4. Non-sustained or sustained atrial and/or ventricular tachyarrhythmias
    5. Atrial fibrillation (including paroxysmal atrial fibrillation) or atrial flutter
    6. Bundle Branch Block, any stable intra-cardiac conduction abnormality with QRS complex > 120 ms, any unstable intra-cardiac conduction abnormality
    7. Sick sinus syndrome, or sinus pauses > 2 seconds
    8. Known atrial and/or ventricular ectopic beats > 10/hour
    9. Fixed second degree AV block, transient or fixed third degree AV block
    10. History of documented ventricular flutter, ventricular fibrillation, Torsade de Pointes tachycardia
    11. Patients who had previously received anthracyclines or other known cardiotoxic medication
  12. Women with breast implants as these may have interfered with the recording of the ECG
  13. Patients with severe electrolyte abnormalities and patients in whom transient electrolyte abnormalities may have been expected during any visit of the study
  14. Patients in whom concomitant neurotropic drug therapy was known to change or was likely to change during the course of the study, where such therapy was likely to affect the patients ERG measurement
  15. Ophthalmic conditions where in the opinion of the investigator they might affect the recording of the ERG
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856336

Sponsors and Collaborators
Antisoma Research
Investigators
Principal Investigator: Mark McKeage The University of Auckland
Principal Investigator: Michael Jameson Waikato Hospital
Principal Investigator: Mark Jeffery Christchurch Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chief Medical Officer, Antisoma Research Limited
ClinicalTrials.gov Identifier: NCT00856336     History of Changes
Other Study ID Numbers: DART
Study First Received: March 4, 2009
Last Updated: March 4, 2009
Health Authority: New Zealand: Medsafe

Additional relevant MeSH terms:
Vadimezan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014