In a phase I clinical trial in cancer patients, the drug involved had one known main adverse effect, which also occurs spontaneously in cancer patients with a fairly high frequency. Experiments in rats have shown marked effects of the drug on tumour growth in high doses, but also dose-dependent toxicity. Consequently, the aim of the study was to determine a dose with a prespecified, acceptable rate of toxicity. As a traditional design could result in inaccurate conclusions, use of the continual reassessment method (CRM) was considered. Twelve dose levels were chosen, allocating to the first patient the lowest, but safe, dose. It is likely that the target dose is far above that, and that CRM then would escalate too fast, skipping certain levels. To ensure that all dose levels inferior to the target dose were tried, some combined methods were proposed: (1) an extension of the design, combining the CRM with a preliminary up-and-down design in order to reach the neighbourhood of the target dose during a successive escalation, and (2) a restriction on the CRM of never escalate more than a single dose level. Simulations showed the extended CRM to be superior by making it possible to investigate a greater range of doses using fewer patients, and to provide more accurate estimates.