Clinical trial NCT00863733: Study of DMXAA (Now Known as ASA404) in Solid Tumors
Official title: Phase I Trial of 5,6 Dimethylxanthenone - 4 - Acetic Acid (DMXAA) in Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Cancer Research UK
Sponsor class: OTHER
Collaborators: name: Cancer Society Auckland
First posted: 2009-03-18
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I study aimed at identifying safe doses of DMXAA in patients with solid tumors.

Detailed description: This is a dose escalation study conducted at a single center in New Zealand. Patients received dimethylxanthenone acetic acid (DMXAA) IV over 20 minutes once every three weeks, up to a maximum of 12 courses.

Cohorts of 3 patients received escalated doses of DMXAA until the maximum tolerated dose (MTD) was determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose limiting toxicity.

Patients had solid tumors for which there was no standard therapy or were refractory to conventional therapy.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed solid tumor that is not amenable to any standard therapy or is refractory to conventional therapy
2. Performance status WHO 0-2
3. Life expectancy greater than 3 months
4. Hemoglobin at least 90 g/L; WBC at least 3,000/mm3; Platelet count at least 100,000/mm3
5. Bilirubin within normal limits; ALT less than 2 times upper limit of normal (ULN); Alkaline phosphatase less than 2 times ULN
6. Creatinine less than 130 umol/L
7. INR and APTT within normal limits
8. Fertile patients must use effective contraception
9. At least 4 weeks since prior anticancer therapy and recovered from toxic effects

Exclusion Criteria:

1. Concurrent malignancy except cone biopsied carcinoma in situ of the cervix and adequately treated basal or squamous cell carcinoma of the skin
2. Other serious medical condition
3. Uncontrolled infection or serious infection within the past 28 days
4. Pregnant or lactating
5. Treatment with glucocorticosteroids within previous two weeks

Primary outcomes:
measure: Toxicity of DMXAA
measure: Maximum tolerated dose of DMXAA
measure: Pharmacokinetics of DMXAA
measure: Effect of DMXAA on coagulation parameters, TNF and other cytokine production, nitric oxide, and serotonin production
Secondary outcomes:
measure: Efficacy of DMXAA
measure: Effect of DMXAA on tumor vasculature
Other outcomes:
Locations:
Study officials:
affiliation: Auckland Hospital
name: Dr Paul Thompson
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jameson MB, Thompson PI, Baguley BC, Evans BD, Harvey VJ, Porter DJ, McCrystal MR, Small M, Bellenger K, Gumbrell L, Halbert GW, Kestell P; Phase I/II Trials Committee of Cancer Research UK. Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer. 2003 Jun 16;88(12):1844-50. doi: 10.1038/sj.bjc.6600992.
citation: 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.