PI-88 in Treating Patients With an Advanced Malignancy (Cancer) or Stage IV Melanoma

NCT ID: NCT00073892

Last Updated: 2022-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2005-11-30

Brief Summary

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.

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.

Conditions

Melanoma (Skin); Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PI-88

Patients receive four consecutive days treatment each week in a 4-week cycle.

Group Type: EXPERIMENTAL

PI-88

Intervention Type: DRUG

250 mg/day injected subcutaneously on four consecutive days each week in a 4- week cycle

Interventions

PI-88

250 mg/day injected subcutaneously on four consecutive days each week in a 4- week cycle

Intervention Type: DRUG

Other Intervention Names

Mannopentaose phosphate sulfate

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medigen Biotechnology Corporation

INDUSTRY

Sponsor Role: collaborator

Cellxpert Biotechnology Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

S. G. Eckhardt, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Cancer Center at University of Colorado Health Sciences Center

Aurora, Colorado, United States

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Queen Elizabeth Hospital

Woodville, South Australia, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Sir Charles Gairdner Hospital - Perth

Perth, Western Australia, Australia

Countries

United States; Australia

Other Identifiers

CDR0000335412

Identifier Type: REGISTRY

Identifier Source: secondary_id

COMIRB-01-207

Identifier Type: -

Identifier Source: secondary_id

PROGEN-PR88201

Identifier Type: -

Identifier Source: org_study_id