Abstract
Alliance A022104/NRG-GI010: A randomized phase II trial testing the efficacy of triplet versus doublet chemotherapy to achieve clinical complete response in patients with locally advanced rectal cancer—The Janus Rectal Cancer trial.
Author
Jesse Joshua Smith
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Jesse Joshua Smith, Arvind Dasari, Qian Shi, Julio Garcia-Aguilar, Hanna Kelly Sanoff, Thomas J. George, Theodore S. Hong, Greg Yothers, Philip Agop Philip, Garth D. Nelson, Tareq Al Baghdadi, Olatunji B. Alese, Eileen Mary O'Reilly, Jeffrey A. Meyerhardt, Ardaman Shergill, Natally Horvat, Paul Bernard Romesser, William A. Hall
Full text
Authors
Jesse Joshua Smith
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Jesse Joshua Smith, Arvind Dasari, Qian Shi, Julio Garcia-Aguilar, Hanna Kelly Sanoff, Thomas J. George, Theodore S. Hong, Greg Yothers, Philip Agop Philip, Garth D. Nelson, Tareq Al Baghdadi, Olatunji B. Alese, Eileen Mary O'Reilly, Jeffrey A. Meyerhardt, Ardaman Shergill, Natally Horvat, Paul Bernard Romesser, William A. Hall
Organizations
Memorial Sloan Kettering Cancer Center, New York, NY, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, and Alliance, Chapel Hill, NC, NRG Oncology and The University of Florida Health Cancer Center, Gainesville, FL, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, NRG Oncology, and The University of Pittsburgh Department of Biostatistics, Pittsburgh, PA, Henry Ford Cancer Institute, Detroit, MI, Mayo Clinic, Rochester, MN, Michigan Cancer Research Consortium, IHA Hematology Oncology, Ypsilanti, MI, Emory University Winship Cancer Institute, Atlanta, GA, Dana-Farber Cancer Institute, Boston, MA, Department of Medicine, Section of Hematology & Oncology, University of Chicago Medical Center, Chicago, IL, Medical College of Wisconsin, Milwaukee, WI
Abstract Disclosures
Research Funding
U.S. National Institutes of Health
U.S. National Institutes of Health
Background:
Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance 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 (pts) 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 pts.
Methods:
In this Alliance for Clinical Trials in Oncology randomized phase II trial (1:1), up to 312 pts 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). Pts 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). Pts 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. This study, activated in late 2022, is open across the NCTN and is actively recruiting. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org. U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov ID: NCT05610163 Clinical trial information: NCT05610163.
Clinical status
Clinical
1 clinical trial
18 organizations
3 drugs
5 targets
Clinical trial
The Janus Rectal Cancer Trial: A Randomized Phase II Trial Testing The Efficacy of Triplet Versus Doublet Chemotherapy to Achieve Clinical Complete Response in Patients With Locally Advanced Rectal CancerStatus: Recruiting, Estimated PCD: 2024-09-01
Organization
Memorial Sloan Kettering Cancer CenterOrganization
The University of Texas MD Anderson Cancer Center, Stem Cell Transplantation Rsch, Houston, TXOrganization
Alliance Statistics and Data CenterOrganization
Mayo ClinicOrganization
University of North Carolina at Chapel HillOrganization
Lineberger Comprehensive Cancer CenterOrganization
NRG OncologyOrganization
The University of Florida Health Cancer CenterOrganization
Harvard Medical SchoolOrganization
Henry Ford Cancer Institute, Detroit, MIOrganization
Michigan Cancer Research ConsortiumOrganization
IHA Hematology Oncology ConsultOrganization
Emory University Winship Cancer InstituteOrganization
Dana-Farber Cancer InstituteOrganization
Medical College of WisconsinDrug
mFOLFOX6Drug
CAPOXDrug
mFOLFIRINOXTarget
VEGFR-1Target
CAPOXTarget
DNATarget
mFOLFOX6