PHASE I TRIAL OF DOCETAXEL AND OXALIPLATIN IN ADVANCED SOLID TUMORS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction Although modest advances have been made in the treatment of advanced solid tumors with the development of new chemotherapies, and targeted therapies, the vast majority of metastatic malignancies remain incurable. In the attempts to further the treatment of such neoplasms, one method of exploration is the combination of anti-tumor agents with potential synergistic, or at least non-overlapping mechanisms of activity in an attempt to forestall the development of tumor resistance to chemotherapy. Rationale for schema and doses As docetaxel has been demonstrated to have an improved therapeutic index when administered weekly, we propose to evaluate the combination of docetaxel administered weekly for two weeks in cycles every three weeks, with oxaliplatin given once every three weeks. Since this regimen of docetaxel is generally well tolerated, we propose to escalate the dose of oxaliplatin towards the dose which is typically used for oxaliplatin as a single agent. We hypothesize that we could potentially maintain, and possibly increase the dose intensity of the docetaxel in combination with oxaliplatin, without requiring the addition of G-CSF. The starting doses in this study will be those recommended for phase II evaluation by Agelaki. However, the total dose of docetaxel per cycle will be divided into doses administered over two weeks, rather than as a single dose. Objectives Primary endpoint: Determination of Maximum Tolerated Dose (MTD) and Recommended Dose for Phase II Study (RP2D) of the combination of oxaliplatin and weekly docetaxel Secondary endpoint: Evaluation of the toxicity of the combination of oxaliplatin and weekly docetaxel Secondary endpoint: Assessment of the anti-tumor activity of the combination of oxaliplatin and weekly docetaxel Secondary endpoint: Assessment of the pharmacokinetics of oxaliplatin and docetaxel Secondary objectives. Toxicity. Descriptive statistics will be used to report the numbers of patients experiencing any toxicity by grade, within each dose. Additionally, special descriptions will be made of toxicities among patients whose dose changed from their original cohort dose assignment. The focus will be on determining whether patients with DLTs are able to tolerate a lower dose once toxicity-related symptoms resolve. Tumor Response. Anti-tumor efficacy of the combination will be reported descriptively.Pharmocokinetic results will be reported descriptively.