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

NCT00130442 | Completed Phase 2 Results DMC

• 1 other identifier: PR88205
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 12

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.

Conditions

Melanoma

Keywords

phase II; metastatic melanoma; dacarbazine; combination; PI-88

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Non-progression Rate

  In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled in cycle 2 and cycle 4.

• Time to 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.

• Duration of Response

  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.

• Survival

  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..

Study Arms (2)

Arm 1- PI-88 plus dacarbazine

EXPERIMENTAL

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

Drug: PI-88 and dacarbazine

Arm 2- dacarbazine alone

ACTIVE COMPARATOR

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

Drug: dacarbazine or DTIC

Interventions

PI-88 and dacarbazine 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 1- PI-88 plus dacarbazine

dacarbazine or DTIC DRUG

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

Arm 2- dacarbazine alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cellxpert Biotechnology Corp.: lead
• Medigen Biotechnology Corporation: collaborator

Study Sites (12)

Arizona Cancer Centre

Tucson, Arizona, 85724, United States

Location

University of Colorado Health Science Centre

Denver, Colorado, 80010-0510, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6307, United States

Location

Sydney Cancer Centre, Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Westmead Institute for Cancer Research

Sydney, New South Wales, 2145, Australia

Location

Wesley Research Institute

Auchenflower, Queensland, 4066, Australia

Location

Townsville Cancer Centre

Townsville, Queensland, 4814, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Border Medical Oncology

Wodonga, Victoria, 3690, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6001, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

phosphomannopentaose sulfate; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director of Regulatory Affairs and Clinical Development
• Organization: Progen Pharmaceuticals Ltd

darrynb@progen-pharma.com

+61 (0)7 38423333

Study Officials

• Michael Millward, MD

  Sir Charles Gairdner Hospital

  STUDY CHAIR

• Anne Hamilton, PhD

  Sydney Cancer Centre

  PRINCIPAL INVESTIGATOR

• Damien Thomson, MD

  Princess Alexandra Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2005
• First Posted: August 15, 2005
• Study Start: June 1, 2005
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: June 23, 2022
• Results First Posted: January 22, 2021

Record last verified: 2022-06

Locations

US (3); AU (9)