The complete phase Ib clinical trial: A method to accelerate new agent development

Abstract

2562 Background: The usual clinical development plan for a new agent (NA) includes a phase I monotherapy trial. However, because many new agents are eventually developed as part of a combination, additional phase I trials assessing the new agent in combination with a standard agent are usually performed (usually as individual phase Ib studies). Our hypothesis was that within a single protocol, several combination phase I trials could be conducted simultaneously. Methods: The design of the protocol is (assuming the new agent is synergistic with an anthracycline, a tubulin interactive agent, an antimetabolite, an angiogenesis inhibitor or an antibody to EGFR): patients with advanced cancer are treated with the combination deemed most likely to be of help-with a choice of a) anthracycline + NA; b) tubulin interactive + NA; c) antimetabolite + NA; d) angiogenesis inhibitor + NA; e) antibody to EGFR + NA. The standard agent is started at full dose with 3 patients placed at 1/3 full dose of NA, 3 patients at 2/3 dose of NA, and 3–6 patients at full dose of the NA in the combination. Results: Our experience with the complete phase Ib trial has found several advantages over conducting separate phase I trials. The advantages include: (a) a very rapid follow-up on preclinical data in one study; (b) a saving of time and expense in the start up; (c) accrual is rapid because many patients in a practice are likely to be eligible (e.g. the standard agent is the standard of care); (d) patients are often less pretreated; (e) the trial generates information for more informed selection of follow-up randomized phase II or III trials. Conclusions: Utilizing a Complete phase Ib trial design is feasible. Our initial experience has suggested that this approach is safe and highly efficient with several potential advantages over multiple sequential combination phase Ib studies. No significant financial relationships to disclose.