eP810 - A Phase 3 Non-Inferiority Randomized Trial Of Neoadjuvant Chemotherapy, Excision And Observation Versus Chemoradiotherapy For Early Rectal

ePoster Presenter(s)

• 

  Carl Brown, MD

  Professor
  St. Paul's Hospital, University of British Columbia
  University of British Columbia
  Vancouver, BC, Canada

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no relevant relationships with ineligible companies.

Author(s)

• CO

  Chris O'Callahan, DVM, MSc, PhD

  Senior Investigator
  Canadian Cancer Trials Group
  Kingston, Ontario, Canada

  Disclosure information not submitted.
• DT

  Dongsheng Tu, PhD

  Senior Biostatistician
  Canadian Cancer Trials Group
  Kingston, Ontario, Canada

  Disclosure information not submitted.
• RL

  Roger Leung, MSc

  Study Coordinator
  Canadian Cancer Trials Group
  Kingston, Ontario, Canada

  Disclosure information not submitted.
• KD

  Kristopher Dennis, MD FRCPC PhD

  Associate Professor
  Division of Radiation Oncology, University of Ottawa
  Ottawa, Ontario, Canada

  Disclosure information not submitted.
• LK

  Lisa Kachnic, MD, FASTRO

  Chu H. Chang Professor of Radiation Oncology
  Columbia University Herbert Irving Comprehensive Cancer Center
  New York, New York, United States

  Disclosure information not submitted.
• JL

  Jonathan M. Loree, MD, FRCPC

  Medical Oncologist
  BCCA-Vancouver Cancer Centre
  Vancouver, British Columbia, Canada

  Disclosure information not submitted.
• MW

  Mark H. Whiteford, Afilliate Professor of Surgery, OHSU

  Director Colorectal Surgery
  The Oregon Clinic. Providence Cancer Institute
  Portland, Oregon, United States

  Disclosure information not submitted.
• WH

  William Hall, MD

  Professor of Radiation Oncology
  Medical College of Wisconsin
  Milwaukee, Wisconsin, United States

  Disclosure information not submitted.
• SC

  Stacey Cohen, MD

  Associate Professor
  Fred Hutchinson Cancer Center
  Seattle, Washington, United States

  Disclosure information not submitted.
• CC

  Christopher Cann, MD

  Assistant Professor
  Fox Chase Cancer Center
  Philadelphia, Pennsylvania, United States

  Disclosure information not submitted.
• NV

  Noam Vanderwalde, MD, MS

  Associate Professor
  West Cancer Center and Research Institute
  Germantown, Tennessee, United States

  Disclosure information not submitted.
• SN

  Steven Nurkin, MD, MS, FACS

  Chair of Colorectal Surgery, Associate Professor of Oncology
  Roswell Park Cancer Center
  Buffalo, New York, United States

  Disclosure information not submitted.
• TJ

  Therese Juul, PhD

  Associate Professor
  Aarhus University
  Aarhus, Midtjylland, Denmark

  Disclosure information not submitted.
• WC

  Winson Cheung, MD, MPH, FRCPC

  Professor of Medicine
  University of Calgary
  Calgary, Alberta, Canada

  Disclosure information not submitted.
• DH

  David Horowitz, MD

  Associate Professor
  Columbia University Herbert Irving Comprehensive Cancer Center
  New York, New York, United States

  Disclosure information not submitted.
• GL

  Gordon Locke, MD

  Clinician
  Ottawa University
  Ottawa, Ontario, Canada

  Disclosure information not submitted.

Senior Author(s)

• 

  Hagen Kennecke, MD, MHA, FRCP

  Medical Director, GI Oncology
  Providence Cancer Center

  Disclosure information not submitted.

Image or Table (Do Not add text here):

Purpose/Background: In early rectal cancer, neoadjuvant therapy combined with transanal endoscopic surgery (TES) results in organ preservation with low rates of local/distant recurrence that are acceptable to many patients. Neoadjuvant chemoradiotherapy (ChemoRT) followed by TES is the best studied option for these patients, with organ preservation of 55-68% and local recurrence in 5-11% of patients. However, perioperative morbidity and functional outcomes are problematic. Recently, neoadjuvant chemotherapy alone combined with TES has shown similar rates of tumor downstaging, organ preservation and local recurrence in a single, phase II study, with excellent surgical outcomes and preserved preoperative function. The purpose of this multicenter randomized controlled trial is to determine whether an initial approach of 3-months of FOLFOX/CAPOX is non-inferior to a standard of pelvic ChemoRT as measured by complete clinical response (cCR) rate and to compare quality of life (QOL) between treatment arms after TES.Methods/Interventions: Patients with cT1-T2/N0M0 pMMR mid-low rectal adenocarcinoma that are deemed locally excisable by the treating surgeon and are medically fit are eligible for enrolment. Exclusion criteria include: high risk histology (mucinous, signet cell, lymphovascular invasion), contraindication to pelvic RT or chemotherapy, ECOG status >2, or inability to comply with surveillance and outcome measures.

Patients will be randomized 1:1 to CAPOX/FOLFOX x 3 months or ChemoRT (54Gy). At 14-16 weeks after treatment initiation, clinical response will be assessed by flexible sigmoidoscopy and MRI. Patients with no response/progression will be recommended radical resection. In all responders, TES is recommended within 8 weeks of last post- treatment assessment for organ preservation. For patients treated by TES, close observation including MRI, endoscopy and CT scan will continue for 5 years post-TES or until recurrence is confirmed.

The co-primary outcome of this study is QOL measured by major low anterior resection syndrome (LARS) at 12 months postop in patients treated by organ preservation.

If the cCR is assumed to be 45% in the ChemoRT arm and the true difference between two arms is 1.6%, then 250 patients are required to be 80% sure that the upper limit of a one-sided 90% confidence interval will exclude a difference in favour of ChemoRT of more than 15%. The threshold for declaring a non-inferior cCR rate, for the omission of ChemoRT, is an observed 7% decrement. With 125 patients per treatment groups, this study would have 80% power to detect a difference of 15% (15% in induction chemotherapy arm and 30% in chemoradiotherapy arm) in the rate of major LARS between two treatment groups at a two-sided 0.1 level.

Secondary outcomes of this study include treatment toxicity, tumor downstaging, 3 year TME free survival, 5 year disease free survival.Results/Outcomes: This study is supported by the National Clinical Trials Network sponsored by the National Cancer Institute. Enrolment is supported within the Canadian Cancer Trials Group (CCTG), The Alliance for Clinical Trials in Oncology group, the ECOG-ACRIN cancer research group, the NRG Oncology group and SWOG Cancer Research Network.

We project 5 patients per month will be randomized between two arms, and a total of 250 patients will be randomized over approximately 4.2 years.Conclusion/

Discussion: If chemotherapy is non-inferior to ChemoRT in achieving cCR and preserves functional outcomes when combined with TES, this would be an exciting new option for these patients with early rectal CA.CO32 - NEO - RT - Study Schema