Challenges of conducting a prospective clinical trial for older patients: Lessons learned from NCCTG N0949 (alliance)

Nadine J. McCleary, Joleen Hubbard, Michelle R. Mahoney, Jeffrey A. Meyerhardt, Daniel Sargent, Alan Venook, Axel Grothey

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Objectives While the risk of developing colorectal cancer increases with age, there are limited prospective data regarding best treatment in the older adult population. We launched a phase III trial to evaluate difference in treatment outcome for older adults (aged ≥ 70 years) with advanced colorectal cancer. Here we review the challenges faced and reasons for poor accrual to N0949. Materials and Methods We describe the conceptualization, development and limited results of N0949, a randomized phase III study of fluoropyrimidine/bevacizumab with or without oxaliplatin (mFOLFOX7 or XELOX) as first line chemotherapy for metastatic colorectal cancer. Fluoropyrimidine was physician choice (e.g., 5-FU/LV or capecitabine). Results Of the projected 380 patients, only 32 patients were enrolled between the study activation in January 2011 until its closure in September 2012. Reasons for poor accrual included eligibility criteria that were too stringent, discomfort with randomizing older patients to regimens of varying intensity without considering their physical fitness, and discomfort with the use of bevacizumab in the older patient population. Several efforts were mounted to design a rationale and age-appropriate study, consider toxicities and varying study practices, and be responsive to stakeholder feedback. Conclusions Challenges were experienced in conducting the first prospective phase III study evaluating progression-free survival of older adults with advanced colorectal cancer receiving palliative chemotherapy with fluoropyrimidine/bevacizumab with or without oxaliplatin in the USA. Future efforts to evaluate treatment outcomes in the older adult population should reflect on lessons learned in this large national effort.

Original languageEnglish (US)
Pages (from-to)24-31
Number of pages8
JournalJournal of Geriatric Oncology
Issue number1
StatePublished - Jan 2018


  • Advanced cancer
  • Advanced colon cancer
  • Advanced colorectal cancer
  • Advanced rectal cancer
  • Bevacizumab
  • Clinical trial
  • Elderly
  • Older adult
  • Oxaliplatin

ASJC Scopus subject areas

  • Oncology
  • Geriatrics and Gerontology


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