Designing Clinical Trials That Accept New Arms: An Example in Metastatic Breast Cancer

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Steffen VentzLorenzo Trippa

Abstract

Purpose The majority of randomized oncology trials are two-arm studies that test the efficacy of new therapies against a standard of care, thereby assigning a large proportion of patients to nonexperimental therapies. In contrast, multiarm studies efficiently share a common control arm while evaluating multiple experimental therapies. A major bottleneck for traditional multiarm trials is the requirement that all therapies-often drugs from different companies-have to be available at the same time when the trial starts. We evaluate the potential gains of a platform design-the rolling-arms design-that adds and removes arms on a rolling basis. Methods We define the rolling-arms design with the goal of minimizing the complexity of random assignment and data analyses of a platform trial. We then evaluate its potential advantages in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Multiple pharmaceutical companies currently test CDK4/6 inhibitors in combination with letrozole in independent two-arm trials. We conducted a simulation study to quantify the reduction in sample size, number of patients treated with the standard of care, and the average time to treatment discovery if these...Continue Reading

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Citations

Mar 9, 2018·Neuro-oncology·Alyssa M VanderbeekBrian M Alexander
Aug 18, 2018·Critical Care Medicine·James P A McCulloughJeffrey J Presneill
Nov 28, 2018·Nature Reviews. Clinical Oncology·Elisabeth G E de VriesSjoukje F Oosting
Mar 4, 2019·Regional Anesthesia and Pain Medicine·Robert GotmakerStephane Heritier
Jan 16, 2019·JAMA Network Open·Steffen VentzLorenzo Trippa
Feb 18, 2020·Clinical Trials : Journal of the Society for Clinical Trials·Babak Choodari-OskooeiMahesh Kb Parmar
May 23, 2019·Statistics in Medicine·Kim May LeeNigel Stallard
Feb 7, 2021·Nature Communications·Steffen VentzLorenzo Trippa
Oct 13, 2020·Contemporary Clinical Trials·Rui WangJoAnn E Manson
Jul 6, 2020·Clinical Therapeutics·Elias Laurin MeyerFranz König
Apr 19, 2021·The Lancet Global Health·Jay J H ParkEdward J Mills
Aug 24, 2021·Clinical Trials : Journal of the Society for Clinical Trials·Subodh SelukarMegan Othus

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