eP816 - A randomized phase-II trial testing triplet versus doublet chemotherapy to achieve complete response in patients with locally advanced rectal cancer

Senior Author(s)

• 

  J. Joshua Smith, MD, PhD

  Associate Attending
  Memorial Sloan Kettering Cancer Center
  MSKCC, Weill Cornell Medical College
  New York, New York, United States

  Disclosure information not submitted.

Author(s)

• AD

  Arvind Dasari, MD, MS

  Associate Professor
  University of Texas MD Anderson Cancer Center
  Houston, Texas, United States

  Disclosure information not submitted.
• QS

  Qian Shi, PhD

  Consultant, Division of Clinical Trials and Biostatistics, Department of Quantitative Health Science
  Mayo Clinic
  Rochester, Minnesota, United States

  Disclosure information not submitted.
• 

  Julio Garcia-Aguilar, MD, PhD (he/him/his)

  Chief Attending
  Memorial Sloan Kettering Cancer Center
  Memorial Sloan Kettering Cancer Center
  New York, New York, United States

  Disclosure information not submitted.
• HS

  Hanna Sanoff, MD, MPH

  Professor of Medicine
  University of North Carolina at Chapel Hill
  Chapel Hill, North Carolina, United States

  Disclosure information not submitted.

ePoster Presenter(s)

• 

  Janet Alvarez, MD (she/her/hers)

  Research Scholar
  Memorial Sloan-Kettering Cancer Center
  New York, NY, United States

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

Author(s)

• WZ

  Wini Zambare, MD

  Memorial Sloan Kettering Cancer Center
  Research Scholar
  New York, New York, United States

  Disclosure information not submitted.
• TG

  Thomas J. George, MD

  Deputy Director
  University of Florida Health Cancer Center
  Gainesville, Florida, United States

  Disclosure information not submitted.
• TH

  Theodore S. Hong, MD

  Radiation Oncologist
  Massachusetts General Hospital Cancer Center; and Harvard Medical School
  Boston, Massachusetts, United States

  Disclosure information not submitted.
• GY

  Greg Yothers, PhD

  Research Professor of Biostatistics
  Department of Biostatistics, University of Pittsburgh School of Public Health; NRG Oncology Statistical and Data Management Center
  Pittsburgh, Pennsylvania, United States

  Disclosure information not submitted.
• PP

  Philip A. Philip, MD, PhD, FRCP

  Medical Oncologist
  Henry Ford Cancer Institute, Wayne University School of Medicine
  Detroit, Michigan, United States

  Disclosure information not submitted.
• GN

  Garth Nelson, MS

  Statistician
  Mayo Clinic
  Rochester, Minnesota, United States

  Disclosure information not submitted.
• TA

  Tareq Al Baghdadi, MD

  Hematology and Oncology
  Trinity Health IHA medical group
  Ypsilanti, Michigan, United States

  Disclosure information not submitted.
• OA

  Olatunji Alese, MD

  Associate Professor & Director of Gastrointestinal Oncology
  Winship Cancer Institute of Emory University
  Atlanta, Georgia, United States

  Disclosure information not submitted.
• EO

  Eileen O'Reilly, MD

  Section Head, Hepatopancreaticobilary & Neuroendocrine Cancers
  Memorial Sloan Kettering Cancer Center
  New York, New York, United States

  Disclosure information not submitted.
• JM

  Jeffrey Meyerhardt, MD, MPH, FASCO

  Professor of Medicine
  Harvard University
  Cambridge, Massachusetts, United States

  Disclosure information not submitted.
• AS

  Ardaman Shergill, MD

  Assistant Professor of Medicine
  The University of Chicago Medicine
  Chicago, Illinois, United States

  Disclosure information not submitted.
• NH

  Natally Horvat, MD, PhD

  Assistant Attending Radiology
  Memorial Sloan Kettering Cancer Center
  New York, New York, United States

  Disclosure information not submitted.
• PR

  Paul Romesser, MD

  Assistant Attending
  Memorial Sloan Kettering Cancer Center
  New York, New York, 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.

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Purpose/Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves adherence with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated it as a primary endpoint. Collaborating with a multidisciplinary oncology team and pt groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation and improve quality of life for patients.Methods/Interventions: In this Alliance for Clinical Trials in Oncology randomized phase II trial (1:1), up to 312 patients with microsatellite stable LARC, clinical stage T4N0, any T, N+ or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course CRT (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks (w) + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 w post-TNT completion for the primary endpoint of cCR per previously validated criteria and recommended WW and surveillance if cCR is achieved or TME if an incomplete response is noted. Secondary objectives include time-to event outcomes (disease-free and overall survival, organ preservation time and time to distant metastasis) and adverse effects. Statistical power, based on cCR, incorporates a one-sided alpha=0.048 and power=90% yielding 312 patients (156 per arm). Biospecimens including archival tumor tissue, matched / normal blood samples and serial rectal MRI will be collected for exploratory correlative research.Results/Outcomes: No results to report.Conclusion/

Discussion: This study, activated in late 2022, is open across the NCTN and has a current recruitment of 226. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org. U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov ID: NCT05610163This study, activated in late 2022, is open across the NCTN and has a current recruitment of 226.The Janus Rectal Cancer Trial Treatment schema