US Oncology Initiates Trial Of Brostallicin Combination Therapy In Advanced Solid Tumors

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Advanced Solid Tumors

Cell Therapeutics, Systems Medicine enrolled the first patient to its complete phase Ib trial of brostallicin used in combination with either bevacizumab or irinotecan, for patients with advanced solid tumors. Combining brostallicin with either bevacizumab or irinotecan is based on existing preclinical data that strongly supports taking these combinations into the clinic. A third treatment arm, which will include brostallicin in combination with an anticancer agent to be identified, will be added to the study. The agent will be identified from ongoing pharmacogenomic investigations using genomic-based search strategies to identify agents that are synergistic with brostallicin.

The trial, being conducted at multiple U.S. Oncology sites, is unique because of the novel "complete" phase I trial design and that genomic-driven discovery is being used to identify at least one of the agents for use with brostallicin. The study design combines a new drug with existing therapies, selected based on genomic profiling, to increase the probability of seeing tumor responses in phase I and may enhance the overall success of the development program. The complete phase I trial design, which was first reported at the 2007 Annual Meeting of the American Society for Clinical Oncology (ASCO), allows several combination phase 1 trials be conducted simultaneously.

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"Most new drug approvals in development are in combination with existing regimens by phase III. By utilizing the complete phase I design, it is possible to rapidly explore several genomicly-guided combinations that could speed the development process and potentially bring benefit to more patients," said Daniel D. Von Hoff, M.D., F.A.C.P., Physician-in-Chief and Director of the Clinical Translational Research Division at the Translational Genomics Research Institute (TGen), Chief Scientific Officer of U.S. Oncology. "With its extensive patient screening at multiple sites, U.S. Oncology is uniquely suited to conduct such studies with a single protocol and parallel multiple regimens."

"Extensive preclinical studies demonstrated that brostallicin is synergistic with multiple agents including both bevacizumab and irinotecan," said James A. Bianco, President and CEO of CTI. "This trial is designed to rapidly follow-up that preclinical data in one consolidated phase I study, save time and expense normally associated with the start up of multiple trials, accrue eligible patients rapidly and generate data to better inform the design of future randomized phase II or III trials."

Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumors models. Brostallicin binds covalently to DNA within the DNA minor groove interfering with DNA division and leading to tumor cell death. More than 200 patients have been treated with brostallicin in single-agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumor types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma met its pre-defined activity and safety hurdles and resulted in a first-line phase II study that is currently being conducted by the European Organization for Research and Treatment of Cancer (EORTC).

Brostallicin was discovered at Pharmacia and developed by Nerviano Medical Sciences (NMS) the largest pharmaceutical research and development facility in Italy and one of the largest oncology-focused, integrated discovery and development companies in Europe. Following a merger between Pfizer and Pharmacia, the rights to Brostallicin were assigned to NMS which continued its development and ultimately licensed worldwide rights to Systems Medicine.

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