  Phase I-II cancer clinical trial designs are intended to accelerate drug
development. In cases where efficacy cannot be ascertained in a short period of
time, it is common to divide the study in two stages: i) a first stage in which
dose is escalated based only on toxicity data and we look for the maximum
tolerated dose (MTD) set and ii) a second stage in which we search for the most
efficacious dose within the MTD set. Current available approaches in the area
of continuous dose levels involve fixing the MTD after stage I and discarding
all collected stage I efficacy data. However, this methodology is clearly
inefficient when there is a unique patient population present across stages. In
this article, we propose a two-stage design for the combination of two
cytotoxic agents assuming a single patient population across the entire study.
In stage I, conditional escalation with overdose control (EWOC) is used to
allocate successive cohorts of patients. In stage II, we employ an adaptive
randomization approach to allocate patients to drug combinations along the
estimated MTD curve, which is constantly updated. The proposed methodology is
assessed with extensive simulations in the context of a real case study.
