Some Notable Properties of the Standard Oncology Phase I Design

Abstract

We identify three properties of the standard oncology phase I trial design or 3 + 3 design.We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the relationship between the standard design and a Bayesian design proposed by Ji et al. (2007). A slight modification to this Bayesian design, under a particular model specification, would assign treatments in a manner identical to the standard design. We finally present calculations revealing the behavior of the standard design in a worst case scenario and compare its behavior with other 3 + 3-like designs.

A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum‐resistant, epithelial ovarian cancer

“…Decitabine was escalated from 10mg/m 2 (dose level 1) to 20mg/m 2 (dose level 2) using the standard 3+3 dose escalation 29. The rationale for this dose schedule was based on previous trials in hematologic cancers demonstrating biological activity in this dose range 12, 13.…”

“…Decitabine was escalated from 10 mg/m 2 (dose level 1) to 20 mg/m 2 (dose level 2), using the standard 3 þ 3 dose escalation. 29 The rationale for this dose schedule was based on previous trials in hematologic cancers demonstrating biological activity in this dose range. 12,13 Dose-limiting toxicity (DLT) was defined as any occurrence during the first 4 weeks of therapy of grade 4 thrombocytopenia, grade 3 or 4 neutropenic fever, grade 4 neutropenia lasting >5 days, grade 3 or 4 nonhematologic toxicity, or failure to recover blood counts by Day 42.…”

“…Two dose levels were used: dose level 1 (10 mg/m 2 ) and 2 (20 mg/m 2 ), and the escalation followed a standard 3 þ 3 design. 29 One patient enrolled at dose level 1 deteriorated rapidly because of progressive disease and received only part of the first treatment cycle. Therefore, this patient was only partly evaluable for assessment of toxicity and was replaced.…”

The Choice of Phase I Bayesian Adaptive Designs in China

“…There have been many discussions on the use of CRM for practical dose-finding trials [4,5]. More recently, mTPI has received much attention and has been successfully implemented for a published clinical trial [6][7][8]. There is a great opportunity to introduce this novel design to trials conducted in China, and we evaluate the feasibility of the application considering the current level of scientific and operational support.…”

Modified BEAM Conditioning Regimen in Patients with Hodgkin and Non-Hodgkin Lymphomas

“…After the first 6 patients were given 200 mg/m² of lomustine, we began to increase the dosage to evaluate probable limitations after a progressive increase to a maximum dosage of 600 mg/m² in a study on typical performance of 3 + 3. 4 To the best of our knowledge, we do not know what is the best regimen for lymphomas autologous transplanted patients. New associations are being studied according to the needs of the different institutions around the world.…”