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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.

Phase 1
18 Years
Not Enrolling
Refractory Tumors

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Trial Information

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.

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)

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:


Principal Investigator

Mark McKeage

Investigator Role:

Principal Investigator

Investigator Affiliation:

The University of Auckland


New Zealand: Medsafe

Study ID:




Start Date:

May 2003

Completion Date:

January 2004

Related Keywords:

  • Refractory Tumors