A Phase I/II Study Of PI-88 In Advanced Malignancies (Phase I), And In Advanced Melanoma(Phase II)
18 Years
N/A
Both
Melanoma (Skin), Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I/II Study Of PI-88 In Advanced Malignancies (Phase I), And In Advanced Melanoma(Phase II)
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.
Inclusion 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
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
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
S. G. Eckhardt, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Colorado, Denver
Authority:
United States: Federal Government
Study ID:
CDR0000335412
NCT ID:
NCT00073892
Start Date:
June 2001
Completion Date:
Related Keywords:
- Melanoma (Skin)
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| University of Colorado Cancer Center at University of Colorado Health Sciences Center | Denver, Colorado 80010 |
