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

NCT ID: NCT00130442

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2010-10-31

Brief Summary

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.

Detailed 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.

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1- PI-88 plus dacarbazine

PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle

Group Type: EXPERIMENTAL

PI-88 and dacarbazine

Intervention Type: DRUG

190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion

Arm 2- dacarbazine alone

dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion

Group Type: ACTIVE_COMPARATOR

dacarbazine or DTIC

Intervention Type: DRUG

intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle

Interventions

PI-88 and dacarbazine

190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion

Intervention Type: DRUG

dacarbazine or DTIC

intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle

Intervention Type: DRUG

Eligibility Criteria

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)

Exclusion Criteria

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medigen Biotechnology Corporation

INDUSTRY

Sponsor Role: collaborator

Cellxpert Biotechnology Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Millward, MD

Role: STUDY_CHAIR

Sir Charles Gairdner Hospital

Anne Hamilton, PhD

Role: PRINCIPAL_INVESTIGATOR

Sydney Cancer Centre

Damien Thomson, MD

Role: PRINCIPAL_INVESTIGATOR

Princess Alexandra Hospital

Locations

Arizona Cancer Centre

Tucson, Arizona, United States

University of Colorado Health Science Centre

Denver, Colorado, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Sydney Cancer Centre, Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Westmead Institute for Cancer Research

Sydney, New South Wales, Australia

Wesley Research Institute

Auchenflower, Queensland, Australia

Townsville Cancer Centre

Townsville, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Border Medical Oncology

Wodonga, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Countries

United States; Australia

Other Identifiers

PR88205

Identifier Type: -

Identifier Source: org_study_id

NCT00128648

Identifier Type: -

Identifier Source: nct_alias