Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	Pharmaceutical / Industry	PROGEN-PR88201 COMIRB-01-207, NCT00073892

Objectives

Phase I

1. Determine the maximum tolerated dose of PI-88 in patients with an advanced malignancy.
2. Determine the safety and tolerability of this drug in these patients.

Phase II

1. Determine the progression-free survival and time to progression in patients with stage IV melanoma treated with this drug.
2. Determine the biological activity of this drug in these patients.

Entry Criteria

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

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

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/mm³
• Platelet count greater than 100,000/mm³
• 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

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

Progen Pharmaceuticals Limited

S. Eckhardt, MD, Principal investigator		Ph: 303-724-3850; 800-473-2288

Registry Information
Official Title		A Phase I/II Study Of PI-88 In Advanced Malignancies (Phase I), And In Advanced Melanoma(Phase II)
Trial Start Date		2001-06-14
Registered in ClinicalTrials.gov		NCT00073892
Date Submitted to PDQ		2003-09-17
Information Last Verified		2004-08-11

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