Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALfilgrastim
filgrastim will be administered at a standard dose and schedule
DRUGPR104
PR104 is administered intravenously once every 21 days
F-18-fluoromisonidazole is administered intravenously prior to performance of PET scan
Sponsors
Proacta, Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of PR-104 | 3 weeks (cycle 1) |
Secondary
| Measure | Time frame |
|---|---|
| Safety profile using CTCAE v3 criteria | — |
| Dose-limiting toxicity of PR-104 | — |
| Pharmacokinetics of PR-104 and its alcohol metabolite in blood | — |
| Anti-tumor activity | — |
| Biomarkers of tumor hypoxia | — |
Countries
New Zealand, United States
Outcome results
None listed