Refractory TumorsPhase 1DARTNCT00856336
Phase I Safety Study of DMXAA in Refractory Tumors
A Phase 1 study testing DMXAA in people with Refractory Tumors, run by Antisoma Research.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Tumors
- What is being tested?
- DMXAA
- Type of treatment
- Injection or infusion
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- May 2003to Jan 2004
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
- Atrial fibrillation (including paroxysmal atrial fibrillation) or atrial flutter
- Bundle Branch Block, any stable intra-cardiac conduction abnormality with QRS complex > 120 ms, any unstable intra-cardiac conduction abnormality
- Sick sinus syndrome, or sinus pauses > 2 seconds
- Known atrial and/or ventricular ectopic beats > 10/hour
- Fixed second degree AV block, transient or fixed third degree AV block
- History of documented ventricular flutter, ventricular fibrillation, Torsade de Pointes tachycardia
- Patients who had previously received anthracyclines or other known cardiotoxic medication
- Women with breast implants as these may have interfered with the recording of the ECG
- Patients with severe electrolyte abnormalities and patients in whom transient electrolyte abnormalities may have been expected during any visit of the study
- 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
- Ophthalmic conditions where in the opinion of the investigator they might affect the recording of the ERG
About this study
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.
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.
Read the 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)
- Conditions
- Refractory Tumors
- Being tested
- DMXAA
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMXAADrug
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)
What is being measured
The primary outcome is the main question the study is designed to answer.
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
To assess the effects of DMXAA on tumour blood flow using dynamic MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2009 (estimated)
- Study startMay 2003
- Primary completionJan 2004
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Refractory TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Antisoma Research
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Mark McKeage, Principal investigator, The University of AucklandMichael Jameson, Principal investigator, Waikato HospitalMark Jeffery, Principal investigator, Christchurch Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00856336
- Sponsor's protocol ID
- DART
- Acronym
- DART
- Status last verified
- Mar 2009
- First submitted
- 4 Mar 2009
- Last updated
- 5 Mar 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16551862Jameson 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.
PubMed 19387077
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00856336
- Acronym / sponsor ID
- DART / DART
- Conditions
- Refractory Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Antisoma ResearchIndustry (pharma, biotech, devices)
- Study start
- May 2003
- Primary completion
- Jan 2004 (actual)
- Study completion
- Jan 2004 (actual)
- First posted
- 5 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DMXAADMXAA, 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) | Drug | – |
Primary outcome
To identify a range of doses for DMXAA where there was either no effect or an acceptably small effect on QTc
6 secondary outcomes
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
To assess the effects of DMXAA on tumour blood flow using dynamic MRI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2009.
- Results publication: PubMed 16551862McKeage 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.
- Derived from this study: PubMed 19387077Jameson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark McKeage principal investigator
The University of Auckland
Michael Jameson principal investigator
Waikato Hospital
Mark Jeffery principal investigator
Christchurch Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DMXAA in people with Refractory Tumors, run by Antisoma Research.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify a range of doses for DMXAA where there was either no effect or an acceptably small effect on QTc. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00856336, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2009.