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

Melanoma Clinical Trial

Official title:

A Phase II Study of PI-88 With Dacarbazine in Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130442
• Other study ID #: PR88205
• Status: Completed
• Phase: Phase 2
• Start date: June 2005
• Est. completion date: October 2010

Study information

• Verified date: June 2022
• Source: Cellxpert Biotechnology Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00128648

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• 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
• dacarbazine or DTIC
intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle

Locations

Country	Name	City	State
Australia	Wesley Research Institute	Auchenflower	Queensland
Australia	Sydney Cancer Centre, Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Australia	Westmead Institute for Cancer Research	Sydney	New South Wales
Australia	Townsville Cancer Centre	Townsville	Queensland
Australia	Border Medical Oncology	Wodonga	Victoria
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
United States	University of Colorado Health Science Centre	Denver	Colorado
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Arizona Cancer Centre	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Cellxpert Biotechnology Corp.	Medigen Biotechnology Corporation

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-progression Rate After Six Cycles	The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles	In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled, up to the end of cycle 6 (About 5 months after randomization)
Secondary	Non-progression Rate	The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after 2 or 4 treatment cycles	In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled in cycle 2 and cycle 4.
Secondary	Time to Progression	treatment was to continue until the subject experienced disease progression.	At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6 . Each cycle was 21 days.Assessed from date of randomization until the date of first documented progression, up to 50 months.
Secondary	Duration of Response	time from commencement to radiological evidence of progression	At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6. Each cycle was 21 days. Assessed from date of randomization until the date of first documented progression, up to 50 months.
Secondary	Survival	time to death and also at time-points 6 month and 12 months	It was to assess time to death. The time frame is at least 6th month, 12th month and data was continuously collected till the end of the study, up to 50 months..