Practical implementation of a modified continual reassessment method for dose-finding trials

Cancer Chemotherapy and Pharmacology
S PiantadosiS Grossman

Abstract

We describe a practical, reliable, efficient dose-finding design for cytotoxic drugs applied in a multi-institutional setting. The continual reassessment method (CRM) was modified for use in phase I trials conducted through the New Approaches to Brain Tumor Therapy (NABTT) Consortium. Our implementation of the CRM uses (1) a simple dose-toxicity model to guide data interpolation, (2) groups of three patients to minimize calculations and stabilize estimates, (3) investigators' clinical knowledge or opinion in the form of data to make the process easier to understand, and (4) a flexible computer program and interface to facilitate calculations. The modified CRM was used in two dose-finding trials of 9-aminocamptothecin in patients with newly diagnosed and recurrent glioblastoma who were taking anticonvulsant medication. The CRM located the maximum tolerated dose (MTD) efficiently in both trials. Compared to conventional designs, the CRM required slightly more than half the number of patients expected, did not greatly overshoot the MTD (i.e. no patients were treated at dangerously high doses), and did not underestimate the MTD. Our experience demonstrates the feasibility of implementing this design in multi-institutional trials an...Continue Reading

Citations

Sep 14, 2002·Statistics in Medicine·William F Rosenberger, Linda M Haines
May 8, 2010·Journal of Neuro-oncology·David M PeereboomUNKNOWN New Approaches to Brain Tumor Therapy (NABTT) Consortium
Aug 28, 2003·Computer Methods and Programs in Biomedicine·Sarah ZoharSylvie Chevret
Jun 13, 2003·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·P F Thall, S-J Lee
Nov 4, 2011·The New England Journal of Medicine·Antonio Di StasiMalcolm K Brenner
Oct 14, 2006·Journal of Biopharmaceutical Statistics·Douglas M Potter
Jun 22, 2013·Journal of Biopharmaceutical Statistics·Guosheng YinJiajing Xu
Feb 4, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S TerakuraUNKNOWN Nagoya Blood and Marrow Transplantation Group
May 14, 2009·Journal of the National Cancer Institute·Christophe Le TourneauLillian L Siu
Aug 27, 2011·Stroke; a Journal of Cerebral Circulation·Magdy SelimUNKNOWN Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators
Mar 1, 2012·Journal of the American Statistical Association·Ying Yuan, Guosheng Yin
Sep 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio JimenoManuel Hidalgo
Dec 15, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Katherine E WarrenLarry E Kun
Jun 26, 2008·Neuro-oncology·Stuart A GrossmanUNKNOWN New Approaches to Brain Tumor Therapy CNS Consortium
Jan 23, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Shubham PantJohanna C Bendell
Nov 11, 2015·Nature Reviews. Clinical Oncology·Kit Man WongS Gail Eckhardt
Oct 1, 2015·Contemporary Clinical Trials·Shengjie YangYuan Ji
Feb 24, 2011·Statistics in Medicine·Emily M Van MeterDipankar Bandyopadhyay
Mar 3, 2011·Statistics in Medicine·Ying Yuan, Guosheng Yin
Feb 6, 2013·International Journal of Cancer. Journal International Du Cancer·K A ThorntonD M Loeb
Feb 18, 2014·British Journal of Clinical Pharmacology·David GuédéRichard Peck
Oct 15, 2013·Statistics in Medicine·Darsy DarssanAnthony N Pettitt
Jan 9, 2015·Annals of Cardiac Anaesthesia·Howard Barkan
Apr 20, 2016·Statistics in Medicine·Alexia IasonosJohn O'Quigley
Jul 10, 2016·Contemporary Clinical Trials·Alexia Iasonos, John O'Quigley
Mar 29, 2001·Journal of Surgical Oncology·P M SimpsonJ S Spratt
Nov 1, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Heather JaceneRichard L Wahl
Oct 29, 2014·Clinical Trials : Journal of the Society for Clinical Trials·Cody ChiuzanSharon D Yeatts
Oct 12, 2010·Clinical Trials : Journal of the Society for Clinical Trials·Yuan JiB Nebiyou Bekele
Feb 7, 2017·Journal of Biopharmaceutical Statistics·Cody ChiuzanShing M Lee
Feb 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leena GandhiCharles M Rudin

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