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

• ClinicalTrials.gov Identifier: NCT00130442
• Recruitment Status: Completed
• First Posted: August 15, 2005
• Results First Posted: January 22, 2021
• Last Update Posted: January 22, 2021
• Sponsor: Medigen Biotechnology Corporation
• Collaborator: Progen Pharmaceuticals
• Information provided by (Responsible Party): Medigen Biotechnology Corporation

Tracking Information

• First Submitted Date: August 12, 2005
• First Posted Date: August 15, 2005
• Results First Submitted Date: October 19, 2020
• Results First Posted Date: January 22, 2021
• Last Update Posted Date: January 22, 2021
• Study Start Date: June 2005
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 29, 2020)

Non-progression Rate After Six Cycles [ Time Frame: 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) ]

The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles

• Original Primary Outcome Measures (submitted: August 12, 2005): The proportion of patients with objective response or stable disease (non-progression rate) after six treatment cycles

Current Secondary Outcome Measures (submitted: December 29, 2020)

• Non-progression Rate [ Time Frame: In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled in cycle 2 and cycle 4. ]
  The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after 2 or 4 treatment cycles
• Time to Progression [ Time Frame: 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. ]
  treatment was to continue until the subject experienced disease progression.
• Duration of Response [ Time Frame: 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. ]
  time from commencement to radiological evidence of progression
• Survival [ Time Frame: 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.. ]
  time to death and also at time-points 6 month and 12 months

Original Secondary Outcome Measures (submitted: August 12, 2005)

• Non-progression rate after two and four treatment cycles
• Time to progression
• Response rate
• Duration of response
• Survival
• Descriptive statistics will be used in the analysis of safety and toxicity endpoints.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
• Official Title: A Phase II Study of PI-88 With Dacarbazine in Patients With Metastatic Melanoma

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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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
• Drug: dacarbazine or DTIC
  intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle

Study Arms

• Experimental: 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
  Intervention: Drug: PI-88 and dacarbazine
• Active Comparator: Arm 2- dacarbazine alone
  dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
  Intervention: Drug: dacarbazine or DTIC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 29, 2020): 134
• Original Enrollment (submitted: August 12, 2005): 118
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

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)
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT00130442
• Other Study ID Numbers: PR88205
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Medigen Biotechnology Corporation
• Study Sponsor: Medigen Biotechnology Corporation
• Collaborators: Progen Pharmaceuticals

Investigators

• Study Chair: Michael Millward, MD; Sir Charles Gairdner Hospital
• Principal Investigator: Anne Hamilton, PhD; Sydney Cancer Centre
• Principal Investigator: Damien Thomson, MD; Princess Alexandra Hospital

• PRS Account: Medigen Biotechnology Corporation
• Verification Date: December 2020