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Accelerating Therapeutic Development through Innovative Trial Design in Colorectal Cancer

  • Lower Gastrointestinal Cancers (AB Benson, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

A Correction to this article was published on 23 April 2018

This article has been updated

Opinion statement

Current trial design is challenged by the advancement of technologies that have enabled deeper understanding of the molecular drivers of colorectal cancer (CRC). The speed of trial testing and the ability to test larger volumes of promising novel agents in the face of smaller populations identified by molecular profiling are challenges posed to clinical studies. Master protocols that utilize umbrella designs are equipped to deal with potential biomarker and matched treatments simultaneously. Although complex in nature, they increase trial efficiency by utilizing shared screening platforms, test multiple treatments together, and simplify regulatory submission and reporting under a common protocol. Emerging technologies such as circulating tumor DNA (ctDNA) may help speed up adjuvant trials. These studies have been traditionally slow to complete due to low event rates and the high numbers needed to recruit. ctDNA used as a surrogate for minimal residual disease (MRD) and as an early marker of relapse may help counter some of these factors that deter innovation in this setting. Finally, in the era of precision medicine, surgery should not be forgotten as the only potentially curative option to date in metastatic disease. Five-year overall survival following resection of liver metastasis exceeds what can be achieved with chemotherapy alone in selected cases. Surgical advances have lowered morbidity and allow for greater resection volumes and repeated interventions. Although historically challenging, a well-designed randomized surgical intervention trial would greatly facilitate moving single-institution guidelines reported by case series into wider clinical practice.

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Change history

  • 23 April 2018

    In the original version of this article, which published in Volume 19, Issue 2 (February 2018), the third author’s name was captured incorrectly. The proper name is now provided.

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Acknowledgements

R01CA184843, R01CA172670, R01CA187238

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard—Unit 0426, Houston, TX, 77030, USA

    Michael Lam MBBS, Jonathan M. Loree MD, Allan Anderson Pereira Lima MD, PhD & Scott Kopetz MD, PhD

  2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yun Shin Chun MD

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Correspondence to Scott Kopetz MD, PhD.

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Michael Lam declares that he has no conflict of interest.

Jonathan M. Loree declares that he has no conflict of interest.

Allan Anderson Pereira Lima declares that he has no conflict of interest.

Yun Shin Chun declares that she has no conflict of interest.

Scott Kopetz has received compensation from Amgen, Array, Bayer, Genentech, MolecularMatch, and Taiho for service as a consultant.

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Lam, M., Loree, J.M., Lima, A.A.P. et al. Accelerating Therapeutic Development through Innovative Trial Design in Colorectal Cancer. Curr. Treat. Options in Oncol. 19, 11 (2018). https://doi.org/10.1007/s11864-018-0524-2

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