- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00073892
PI-88 in Treating Patients With an Advanced Malignancy (Cancer) or Stage IV Melanoma
A Phase I/II Study Of PI-88 In Advanced Malignancies (Phase I), And In Advanced Melanoma(Phase II)
RATIONALE: PI-88 may stop the growth of cancer by stopping blood flow to the tumor.
PURPOSE: Phase I/II trial to study the effectiveness of PI-88 in treating patients who have an advanced malignancy (cancer) or stage IV melanoma.
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
Phase I
- Determine the maximum tolerated dose of PI-88 in patients with an advanced malignancy.
- Determine the safety and tolerability of this drug in these patients.
Phase II
- Determine the progression-free survival and time to progression in patients with stage IV melanoma treated with this drug.
- Determine the biological activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Phase I (parts 1 and 2):
- Part 1: Patients receive PI-88 subcutaneously (SC) once daily on days 1-4 and 15-18.
Cohorts of 3-6 patients receive escalating doses of PI-88 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD has been determined in part I, the effect of dose frequency is determined in patients in part II.
- Part 2: Patients receive PI-88 SC once daily on days 1-4, 8-11, 15-18, and 22-25 at a dose based on the MTD determined in part 1.
Cohorts of 3 patients receive escalating doses of PI-88 until the MTD at this frequency is determined.
- Phase II (patients with metastatic melanoma): Patients receive PI-88 as in phase I, part 2 at the MTD.
Treatment in both phases repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 18-69 patients (18-30 for phase I [part 1], 6-9 for phase I [part 2], and 25-30 for phase II) will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Queensland
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Brisbane, Queensland, Australia, 4102
- Princess Alexandra Hospital
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South Australia
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Woodville, South Australia, Australia, 5011
- Queen Elizabeth Hospital
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Victoria
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Melbourne, Victoria, Australia, 3004
- Alfred Hospital
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Western Australia
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Perth, Western Australia, Australia, 6009
- Sir Charles Gairdner Hospital - Perth
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-
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Colorado
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Aurora, Colorado, United States, 80010
- University of Colorado Cancer Center at University of Colorado Health Sciences Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Phase I
- Histologically or cytologically confirmed malignancy
- No other effective treatment available OR failed prior therapy
- No prior or concurrent symptomatic or known CNS involvement or brain or meningeal metastases
Phase II
- Diagnosis of stage IV melanoma
- Metastatic disease must be measurable
- No other effective treatment available OR failed prior therapy
- Asymptomatic brain metastases allowed provided patient is off steroids
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 70-100%
Life expectancy
- At least 3 months
Hematopoietic
- Neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
- Negative serotonin release assay test for anti-heparin antibodies
- No other abnormal bleeding tendency
- No history of heparin-induced thrombocytopenia
- No history of immune-mediated thrombocytopenia
- No history of thrombolytic thrombocytopenic purpura
- No history of other platelet disease
Hepatic
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- AST and ALT no greater than 2 times ULN (5 times ULN if liver metastases are present)
- PTT normal (20-34 sec)
- PT less than 1.5 times ULN
Renal
- Creatinine clearance greater than 60 mL/min OR
- Glomerular filtration rate greater than 60 mL/min
Cardiovascular
- No myocardial infarction within the past 3 months
- No stroke within the past 3 months
- No congestive heart failure within the past 3 months
Gastrointestinal
- No history of acute or chronic gastrointestinal bleeding within the past 2 years
- No inflammatory bowel disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No AIDS-related illness
- No serious infection within the past 4 weeks
- No history of alcohol, drug, or other substance abuse
- No history of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents (e.g., heparin)
- No risk of bleeding due to open wounds or planned surgery
- No clinically significant nonmalignant disease
- No uncontrolled infection
Inclusion Criteria
- Current diagnosis of metastatic melanoma, where other effective therapy was not available or had failed.
- Measurable disease. Metastatic lesions had to have been measurable by MRI or CT, and cutaneous lesions by physical examination.
- Biopsiable Lesion Group only: Must have had at least one biopsiable lesion that was bi-dimensionally measurable and previously unirradiated.
- Age≥ 18 years.
- Have voluntarily given written informed consent to participate in this study.
- Performance status: ECOG 0 - 2 (Karnofsky 70 -100%).
- Life expectancy of at least 3 months.
- Neutrophil count > 1.5 x 109/L (1,500/mm3).
- Platelet count > 100 x 109/L (100,000/mm3).
- APTT normal (20 - 34 sec).
- PT <1.5 x ULN.
- Calculated creatinine clearance, using the Cockcroft-Gault formula, >60 mL/min. If just below 60 mL/min, then GFR>60 mL/min as determined by EDTA or DTPA scan.
- Bilirubin <1.5 x ULN.
- AST and ALT up to 2 x ULN; except in the presence of liver metastases; up to 5 x ULN.
Exclusion Criteria
- Current symptomatic central nervous system involvement, or active brain or meningeal metastases.
- Concomitant use of aspirin (> 100 mg/day), non-steroidal anti-inflammatory drugs (with the exception of COX-2 inhibitors), heparin, low molecular weight heparin or warfarin (> 1 mg/day) which was ongoing or anticipated during the study period. Low-dose aspirin (100 mg/day or less) or low-dose warfarin (1 mg/day or less) was permitted.
- Heparin or low molecular weight heparin within the previous 2 weeks.
- Chemotherapy, investigational therapy or hormonal therapy in the previous 4 weeks.
- Radiotherapy to a major bone marrow bearing area such as pelvis, femoral heads, lumbar-sacral spine, within the previous 4 weeks. Radiotherapy to other sites within the previous 2 weeks.
- History of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents, especially heparin.
- History of heparin-induced thrombocytopenia, immune mediated thrombocytopenia, thrombotic thrombocytopenic purpura and/or other platelet diseases, or laboratory evidence of anti-heparin antibodies.
- Myocardial infarction, stroke or congestive heart failure within the previous 3 months
- History of acute or chronic gastrointestinal bleeding within the previous two years, inflammatory bowel disease, any other abnormal bleeding tendency, or patients at risk of bleeding due to open wounds or planned surgery.
- Uncontrolled infection or serious infection within the previous 4 weeks.
- Clinically significant non-malignant disease.
- Known AIDS-related illness or HIV positive.
- Women who were pregnant, breast feeding, or of childbearing potential in whom pregnancy could not be excluded.
- History of abuse of alcohol, drugs or other substances.
- Not recovered from major surgery if conducted prior to the study.
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 4 weeks since prior chemotherapy
Endocrine therapy
- More than 4 weeks since prior hormonal therapy
Radiotherapy
- More than 2 weeks since prior radiotherapy
- More than 4 weeks since prior radiotherapy to a major bone-marrow bearing area (e.g., pelvis, femoral heads, or lumbar-sacral spine)
- Concurrent palliative radiotherapy allowed
Surgery
- Recovered from prior major surgery
- No concurrent surgery
Other
- More than 2 weeks since prior heparin or low-molecular weight heparin
- More than 4 weeks since other prior investigational therapy
- No other concurrent investigational drugs
- No other concurrent antineoplastic therapy
- No concurrent aspirin or aspirin-containing medications
No concurrent nonsteroidal anti-inflammatory drugs
- Concurrent cyclooxygenase-2 inhibitors allowed
- No concurrent heparin or low-molecular weight heparin
- No concurrent warfarin or warfarin-containing medications
- No other concurrent anticoagulant medications
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PI-88
Patients receive four consecutive days treatment each week in a 4-week cycle.
|
250 mg/day injected subcutaneously on four consecutive days each week in a 4- week cycle
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy Analysis
Time Frame: end of Cycle 6 of study treatment (24 weeks)
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non-progression rate (objective response or stable disease)
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end of Cycle 6 of study treatment (24 weeks)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy Analysis
Time Frame: were time to progressive disease, survival, duration of partial response, complete response and stable disease
|
time to progression and overall survival
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were time to progressive disease, survival, duration of partial response, complete response and stable disease
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: S. G. Eckhardt, MD, University of Colorado, Denver
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PROGEN-PR88201
- CDR0000335412 (Registry Identifier: PDQ (Physician Data Query))
- COMIRB-01-207
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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