pr104 and g-csf in treating patients with solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy, such as pr-104, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. colony-stimulating factors, such as g-csf, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. giving pr-104 together with g-csf may kill more tumor cells. purpose: this phase i trial is studying the side effects and best dose of pr-104 when given together with g-csf in treating patients with solid tumors.

objectives: primary * determine the maximum tolerated dose of pr-104 in combination with filgrastim (g-csf) in patients with solid tumors. secondary * characterize the safety of this regimen in these patients. * evaluate the pharmacokinetics of pr-104 and its alcohol metabolite. * evaluate the rate of hypoxia in various solid tumors using f-miso pet (18f-fluoromisonidazole positron emission tomography) imaging. * assess for antitumor toxicity in these patients. * collect plasma samples for the assessment of potential biomarkers of tumor hypoxia. outline: this is a multicenter, dose-escalation study of pr-104. patients receive pr-104 iv over 1 hour on day 1 and filgrastim (g-csf) on day 2. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. patients also undergo 18f-fluoromisonidazole pet scans at baseline and prior to course 3 to assess tumor hypoxia. patients undergo blood sample collection periodically during course 1. samples are analyzed for the pharmacokinetics of pr-104 and for identification of biomarkers for tumor hypoxia. after completion of study treatment, patients are followed at 30 days.

Eligibility 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

Keywords: unspecified adult solid tumor, protocol specific