A Phase I, Multi-Center, Open-Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR104 Given With Prophylactic G-CSF in Subjects With Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumors

- Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-1

- Absolute neutrophil count ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Hemoglobin ≥ 9 g/dL (no red blood cell transfusions allowed)

- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

- PTT ≤ 1.5 times normal

- Serum creatinine ≤ 1.5 times ULN

- ALT or AST ≤ 2 times ULN (≤ 5 times ULN if liver metastases are present)

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 30 days after
completion of study therapy

- Able to read, understand, and provide written informed consent

Exclusion criteria:

- Evidence of a significant medical disorder or laboratory finding that, in the opinion
of the investigator, compromises the patient's safety during study participation,
including any of the following:

- Uncontrolled infection or infection requiring a concomitant parenteral
antibiotic

- Uncontrolled diabetes

- Congestive heart failure

- Myocardial infarction within the past 6 months

- Chronic renal disease

- Coagulopathy (excluding prophylactic anticoagulation)

- Known HIV positivity

- Hepatitis B sAg-positive or known to be hepatitis C-positive with abnormal liver
function tests

PRIOR CONCURRENT THERAPY:

- No more than 3 prior myelosuppressive chemotherapy regimens

- Patients who have received more than 3 prior myelosuppressive regimens may be
eligible, if considered to have adequate marrow, based on prior exposure to 1 of
the following regimens:

- Minimally myelosuppressive regimens

- Limited courses of myelosuppressive regimens

- More than 4 weeks since prior and no other concurrent licensed or investigational
anticancer treatment (6 weeks for nitrosoureas or mitomycin C)

- More than 24 hours since any prior radiotherapy and no likelihood of toxicity from
this therapy

- More than 4 weeks since major surgery

- No prior radiotherapy to > 20% of bone marrow

- No prior high-dose chemotherapy (including either myeloablative or non-myeloablative
transplantations)

- Prior and concurrent androgen deprivation therapy allowed

- Concurrent systemic steroids allowed, provided the patient has been on a stable dose
for at least 2 weeks prior to first dose of PR-104

- No concurrent irradiation therapy (palliative or therapeutic), unless given in the
absence of tumor progression