Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma

Cellxpert Biotechnology

Status and phase

Completed

Phase 2

Conditions

Melanoma

Treatments

Drug: PI-88 and dacarbazine

Drug: dacarbazine or DTIC

Study type

Interventional

Funder types

Industry

Identifiers

NCT00130442

PR88205

Details and patient eligibility

About

The aim of the study is to compare the safety and effectiveness of a new drug called PI-88, when used in combination with an approved chemotherapy drug called dacarbazine, in the treatment of metastatic melanoma.

PI-88 blocks new blood vessel growth in tumours (starves it of nutrients) and dacarbazine stops the cancer cells from growing. The results from this study will be analysed to see if it is worthwhile for the two drugs to be tested in future studies involving larger numbers of melanoma patients.

Full description

Metastatic melanoma is a difficult-to-treat cancer for which available treatment options are limited and minimally effective. Dacarbazine is currently one of the standard chemotherapy drugs used for the treatment of metastatic melanoma. However, it is associated with low response rates (10-20%) and median survival of less than 12 months (6-11 months in most studies). PI-88 is an antiangiogenic and antimetastatic drug that has already shown some evidence of efficacy when used alone in an intermittent dosage regimen (4 consecutive days per week) in the treatment of patients with advanced melanoma. The FDA has designated PI-88 as an Orphan Drug for this indication, as well as for Stage III and high-risk stage II disease. The aim of this randomised pilot phase II trial is to determine whether PI-88 in combination with a standard regimen of dacarbazine (1000 mg/m2 every 3 weeks) should be considered for further investigation in a larger-scale trial.

Enrollment

134 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically proven metastatic melanoma
Surgery not feasible or inappropriate
Measurable disease. Metastatic lesions must be measurable by magnetic resonance imaging (MRI) or computed tomography (CT) as defined in Response Evaluation Criteria in Solid Tumors (RECIST), and cutaneous lesions by physical examination.
Have voluntarily given written informed consent to participate in this study
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
Life expectancy at least 3 months
Neutrophil count > 1.5 x 10^9/L (1,500/mm3)
Platelet count > 100 x 10^9/L (100,000/mm3)
Acceptable liver function tests (see Exclusion Criteria for maximum allowable elevations of ALT, AST, ALP and LDH)
PT < 1.5 x upper limit of normal (ULN)
APTT < 1.5 x ULN
Creatinine clearance > 40 mL/min, calculated using the Cockcroft-Gault formula (if just below 40 mL/min, then GFR > 40 mL/min as determined by 24-hour urine collection)

Exclusion criteria

Current or history of central nervous system involvement, brain or meningeal metastases
Ocular melanoma
Clinically significant non-malignant disease
Prior or co-existent malignancies (other than stage I internal malignancy where treated and disease-free for > 5 years, non-melanomatous skin cancer or in situ cancer of the cervix)
Prior chemotherapy
Prior treatment with vaccines and/or biological response modifiers within the previous 4 weeks
Prior treatment with radiotherapy within the previous 4 weeks (local palliative radiotherapy is permitted)
Radiotherapy to > 30% of marrow-bearing bone within the previous 3 months
Major surgery within the past 4 weeks
Concomitant use of aspirin (> 150 mg/day), non-steroidal anti-inflammatory drugs (except specific COX-2 inhibitors), heparin, low molecular weight heparin, warfarin (> 1 mg/day) or anti-platelet drugs (abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (≤ 150 mg/day) and low-dose warfarin (≤ 1 mg/day) are permitted as concomitant medications.
Heparin or low molecular weight heparin within the previous 2 weeks
History of acute or chronic gastrointestinal bleeding within the last 2 years, inflammatory bowel disease or other abnormal bleeding tendency
Patients at risk of bleeding due to open wounds or planned surgery
Bilirubin > 1.5 x ULN
AST or ALT > 3 x ULN unless patient has hepatic metastases
LDH > 2 x ULN
Alkaline phosphatase > 5 x ULN, unless patient has bone metastases
Myocardial infarction, stroke or congestive heart failure within the past 3 months
Women who are pregnant or breast feeding
Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception
History of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents, especially heparin
History of immune-mediated thrombocytopenia, thrombotic thrombocytopenic purpura or other platelet disease, or laboratory evidence of anti-heparin antibodies
Uncontrolled or serious infection within the past 4 weeks
Patients who are unable to be compliant or to follow instructions given to them by clinic staff