MelanomaPhase 2NCT00130442
Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
A Phase 2 study testing PI-88 and dacarbazine and dacarbazine or DTIC in people with Melanoma, run by Cellxpert Biotechnology Corp. at 12 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- PI-88 and dacarbazine and dacarbazine or DTIC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Jun 2005to Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Australia9 sites
Wesley Research Institute
Auchenflower, Queensland, 4066
Sydney Cancer Centre, Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Royal Perth Hospital
Perth, Western Australia, 6001
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009
Westmead Institute for Cancer Research
Sydney, New South Wales, 2145
Townsville Cancer Centre
Townsville, Queensland, 4814
Border Medical Oncology
Wodonga, Victoria, 3690
The Queen Elizabeth Hospital
Woodville, South Australia, 5011
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
United States3 sites
University of Colorado Health Science Centre
Denver, Colorado, 80010-0510
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6307
Arizona Cancer Centre
Tucson, Arizona, 85724
About this study
Official title: A Phase II Study of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
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.
Read the 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
- Being tested
- PI-88 and dacarbazine, dacarbazine or DTIC
- Keywords
- phase II, metastatic melanoma, dacarbazine, combination, PI-88
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PI-88 and dacarbazineDrug
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 DTICDrug
intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: dacarbazine or DTIC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-progression Rate After Six Cycles
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles
Measured: 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
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after 2 or 4 treatment cycles
Measured: 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
treatment was to continue until the subject experienced disease progression.
Measured: 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
time from commencement to radiological evidence of progression
Measured: 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
time to death and also at time-points 6 month and 12 months
Measured: 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..
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2005 (estimated)
- Study startJun 2005
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cellxpert Biotechnology Corp.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medigen Biotechnology Corporation
- Responsible party
- Sponsor
- Investigators
- Michael Millward, MD, Study chair, Sir Charles Gairdner HospitalAnne Hamilton, PhD, Principal investigator, Sydney Cancer CentreDamien Thomson, MD, Principal investigator, Princess Alexandra Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00130442
- Sponsor's protocol ID
- PR88205
- Status last verified
- Jun 2022
- First submitted
- 12 Aug 2005
- Last updated
- 23 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00130442
- Acronym / sponsor ID
- PR88205
- Conditions
- Melanoma
- Keywords
- phase II, metastatic melanoma, dacarbazine, combination, PI-88
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Cellxpert Biotechnology Corp.Industry (pharma, biotech, devices)
- Collaborators
- Medigen Biotechnology Corporation
- Study start
- Jun 2005
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 15 Aug 2005 (estimated)
- Results
- Posted 22 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1- PI-88 plus dacarbazine | Experimental | Drug: PI-88 and dacarbazinePI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle |
| Arm 2- dacarbazine alone | Active comparator | Drug: dacarbazine or DTICdacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PI-88 and dacarbazine190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion | Drug | Arm 1- PI-88 plus dacarbazine |
| dacarbazine or DTICintravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle | Drug | Arm 2- dacarbazine alone |
Primary outcome
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
4 secondary outcomes
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.
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.
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.
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..
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Millward, MD study chair
Sir Charles Gairdner Hospital
Anne Hamilton, PhD principal investigator
Sydney Cancer Centre
Damien Thomson, MD principal investigator
Princess Alexandra Hospital
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PI-88 and dacarbazine and dacarbazine or DTIC in people with Melanoma, run by Cellxpert Biotechnology Corp. at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2022.