Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
Status:
Terminated
Trial end date:
2010-05-01
Target enrollment:
Participant gender:
Summary
The current understanding of PR104 justifies the evaluation of PR104 with docetaxel in
subjects with Non Small Cell Lung Cancer (NSCLC). These include:
- Aldo-keto reductase 1C3 (AKR1C3). NSCLC has been shown to express high levels of AKR1C3
in about one half of tumors tested. Subjects with high levels of AKR1C3 should have
increased activation of PR104 within their tumor.
- Hypoxia. NSCLC has been demonstrated to be a tumor with hypoxia based on both direct
tumor measurements (oxygen electrodes) and hypoxic positron emission tomography (PET)
imaging. Tumor hypoxia in NSCLC should be sufficient to activate PR104 to its active
metabolites PR104H and PR104M.
- Preclinical data. The use of docetaxel and PR104 alone and in combination in preclinical
models demonstrates activity of PR104 as a single agent and supraadditive activity when
PR104 and docetaxel are used in combination.
- Manageable toxicity. PR104 and docetaxel with Granulocyte Colony-stimulating Factor
(G-CSF) have been combined in a prior phase I study. A Maximum Tolerated Dose (MTD) has
been identified and the major toxicities of this combination are understood.
The current study will provide an estimate of the activity of PR104 in subjects with NSCLC.
This information will prove valuable in defining the future clinical development of PR104,
and in determining if PR104 has sufficient activity in NSCLC to warrant a larger phase III
registration study in this indication.
Primary objectives
• Estimate the response rate (RR) of PR104/docetaxel
Secondary objectives
- Evaluate survival
- Evaluate progression free survival (PFS)
- Evaluate time to progression (TTP)
- Evaluate safety
- Evaluate the pharmacokinetics of PR104 and its metabolites
- Evaluate the pharmacokinetics of docetaxel
- Evaluate the tumor hypoxia using 18F-fluoromisonidazole (18F-MISO) PET imaging
- Collect diagnostic biopsy samples for the determination of AKR1C3
- Collect plasma samples for assessment of potential biomarkers of tumor hypoxia