PHASE I TRIALS OF ANTICANCER AGENTS

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DESCRIPTION: (Applicant's Description) The introduction of new antineoplastic therapies into clinical trials remains one of the most important areas of investigation in clinical oncology. To assure continued progress in the care and treatment of patients with cancer, investigators will need to build on the existing therapeutic approaches by the introduction of new agents and modalities into these programs. For new agents to progress smoothly through early clinical trials it is imperative that they be evaluated in centers where timely and reliable studies can be performed which provide maximum information a b o u t the clinical characteristics and toxicities of the therapy, pharmacology, and relevant biologic endpoints. This proposal will outline the capability of the investigators utilizing the facilities and resources of the Hopkins Oncology Center to perform high quality scientifically based phase I clinical an pharmacologic studies of new agents in patients with solid tumors and hematologic malignancies. The specific aims of the trials proposed are as follows: 1) To define the maximum tolerated dose and an appropriate dose and schedule for further evaluation of efficacy in phase II studies. The acute and chronic toxicities will be evaluate and quantitated. Toxicities may be redefined when agents are given in combination with other therapeutic drugs or agents such as colony stimulating factors or other agents capable of modifying toxicity. 2) To p e r f orm detailed studies of the pharmacology, pharmacokinetics, and pharmacodynamics of the therapeutic agents under study and when possible to explore these characteristics in special patient populations such as impaired end organ function, or to evaluate for differences based on age, gender, or race and ethnic group. 3) To incorporate ancillary laboratory studies which are performed on clinical patient material or performed in parallel to the clinical studies which enhance the understanding of toxicity or biochemical and molecular mechanisms of drug effect, and the relationship between drug administration and biological changes in treated patients. Performance of each of these tasks requires an expertise of its own but it is important they be considered together. This proposal will detail the elements as they exist at Johns Hopkins to perform this work.