Ethical considerations for outcome-adaptive trial designs: a clinical researcher's perspective.

In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as 'outcome-adaptive randomization.' In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior.

Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.

Background: Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy.

Methods: In this unmasked, open-label randomised phase 3 trial we enrolled patients with metastatic, unresectable, or locally advanced NSCLC from 121 sites in Canada and the USA.

Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck.

Purpose: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes.

Treatment rationale and study design for a randomized trial of pemetrexed/carboplatin followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab in patients with advanced non-small-cell lung cancer of nonsquamous histology.

Herein we describe a companion ongoing randomized phase III study in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). Patients with chemotherapy-naive advanced disease will be randomized to receive either pemetrexed 500 mg/m2 plus carboplatin area under the curve (AUC) 6 for 4 cycles followed by maintenance pemetrexed (arm A) or paclitaxel 200 mg/m2 plus carboplatin AUC 6 plus bevacizumab 15 mg/kg for 4 cycles followed by maintenance bevacizumab (arm B). Cycles are 3 weeks.