Stage II Rectal Cancer AJCC v8Phase 2/3JANUSNCT05610163
Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation and Continuing Response
A Phase 2/3 study testing Capecitabine, 5-fluorouracil and Leucovorin calcium in people with Stage II Rectal Cancer AJCC v8 and Stage III Rectal Cancer AJCC v8, run by Alliance for Clinical Trials in Oncology at 685 sites in 2 countries.
Trial summary
This phase II/III trial compares the effect of usual treatment approach alone (FOLFOX or CAPOX after chemoradiation) with using FOLFIRINOX after chemoradiation in patients with stage II-III rectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage II Rectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Locally Advanced Rectal Adenocarcinoma
- What is being tested?
- Capecitabine, 5-fluorouracil and Leucovorin calcium
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 760 participants
- Where
- 685 sitesin 2 countries
- Study dates
- 8 Dec 2022to 1 Jul 2037
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic Documentation: rectal adenocarcinoma, mismatch repair proficient (pMMR)
- Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection (APR) or coloanal anastomosis
- Tumor site: Rectum; distal edge of the tumor =< 12cm from the anal verge (as determined by surgeon's endoscopic assessment; MRI can be used to compliment this information, but endoscopy should be the primary means of assessment)
- No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer within the past 5 years is allowed. No local approaches to excising the rectal cancer (even if done for diagnostic purposes) are allowed (e.g., transanal excision [open or minimally invasive], local excision, endoscopic submucosal dissection or endoscopic submucosal resection).
- Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
- Therefore, for women of childbearing potential only, a negative pregnancy test (urine or serum according to institutional guidelines) done =< 14 days prior to registration is required. Female subjects agree to use highly effective contraception combined with an additional barrier method (e.g, diaphragm, with a spermicide) while on study and for >= 9 months after last dose of study drug, and the same criteria are applicable to male subjects if they have a partner of childbirth potential. Male subject agrees to use a condom and not donate sperm while in this study and for >= 6 months after the last treatment
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- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (or Karnofsky >= 60%)
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm
- Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 50 mL/min
- ^3
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
- No upper rectal tumors (i.e., distal portion of tumor must be => 12 cm from the anal verge)
- No recurrent rectal cancer; prior transanal excision, prior distal sigmoid cancer with a low anastomosis or prior endoscopic submucosal dissection
- No known mismatch repair deficient rectal adenocarcinoma
- HIV-infected patients on effective anti-retro viral therapy with undetectable viral load within 6 months are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification1. To be eligible for this trial, patients should be class 2B or better
- Testing for dihydropyrimidine dehydrogenase (DPD) deficiency is not required. However, when available, patients with complete lack of DPD should not be treated with fluoropyrimidines (such patients must not be enrolled or if initiated on therapy and noted to have fluoropyrimidine related toxicities be taken off protocol; dose reductions for patients with partial deficiency may be done per local guidelines
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
- Once systemic chemotherapy has been completed and the patient is either in surveillance or being considered for surgery then medically necessary CYP3A4 medications can be resume
Who cannot join
None listed.
Trial locations and contacts
685 sites in 2 countries.
306 sites in 2 countries
United States300 sites
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Queen's Cancer Center - Pearlridge
‘Aiea, Hawaii, 96701
The Cancer Center of Hawaii-Pali Momi
‘Aiea, Hawaii, 96701
The Queen's Medical Center - West Oahu
‘Ewa Beach, Hawaii, 96706
Avera Cancer Institute-Aberdeen
Aberdeen, South Dakota, 57401
Providence Regional Cancer System-Aberdeen
Aberdeen, Washington, 98520
Atrium Health Stanly/LCI-Albemarle
Albemarle, North Carolina, 28002
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
AdventHealth Altamonte
Altamonte Springs, Florida, 32701
OSF Saint Anthony's Health Center
Alton, Illinois, 62002
UPMC Altoona
Altoona, Pennsylvania, 16601
The Don and Sybil Harrington Cancer Center
Amarillo, Texas, 79106
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, 98508
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, 99508
Alaska Oncology and Hematology LLC
Anchorage, Alaska, 99508
Alaska Women's Cancer Care
Anchorage, Alaska, 99508
Anchorage Oncology Centre
Anchorage, Alaska, 99508
Katmai Oncology Group
Anchorage, Alaska, 99508
Providence Alaska Medical Center
Anchorage, Alaska, 99508
AnMed Health Cancer Center
Anderson, South Carolina, 29621
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California, 93420
PCR Oncology
Arroyo Grande, California, 93420
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Rush-Copley Medical Center
Aurora, Illinois, 60504
Advocate Outpatient Center - Aurora
Aurora, Illinois, 60506
Mount Sinai Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237
MedStar Good Samaritan Hospital
Baltimore, Maryland, 21239
Advocate Good Shepherd Hospital
Barrington, Illinois, 60010
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania, 15009
Indu and Raj Soin Medical Center
Beavercreek, Ohio, 45431
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Saint Charles Health System
Bend, Oregon, 97701
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Billings Clinic Cancer Center
Billings, Montana, 59101
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Saint Elizabeth Boardman Hospital
Boardman, Ohio, 44512
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Boston Medical Center
Boston, Massachusetts, 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
United Hospital Center
Bridgeport, West Virginia, 26330
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215
NYU Langone Hospital - Brooklyn
Brooklyn, New York, 11220
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Keck Medicine of USC Buena Park
Buena Park, California, 90621
Roswell Park Cancer Institute
Buffalo, New York, 14263
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
UPMC Camp Hill
Camp Hill, Pennsylvania, 17011
Illinois CancerCare-Canton
Canton, Illinois, 61520
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Aultman Health Foundation
Canton, Ohio, 44710
Mercy Cancer Center - Cape Girardeau
Cape Girardeau, Missouri, 63703
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
Carlisle Regional Cancer Center
Carlisle, Pennsylvania, 17015
Mercy Cancer Center - Carmichael
Carmichael, California, 95608
Mercy San Juan Medical Center
Carmichael, California, 95608
Caro Cancer Center
Caro, Michigan, 48723
SIH Cancer Institute
Carterville, Illinois, 62918
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Duke Cancer Center Cary
Cary, North Carolina, 27518
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
AdventHealth Celebration
Celebration, Florida, 34747
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio, 45459
Centralia Oncology Clinic
Centralia, Illinois, 62801
Saint Mary's Hospital
Centralia, Illinois, 62801
Providence Regional Cancer System-Centralia
Centralia, Washington, 98531
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Atrium Health Pineville/LCI-Pineville
Charlotte, North Carolina, 28210
Levine Cancer Institute-SouthPark
Charlotte, North Carolina, 28211
Atrium Health University City/LCI-University
Charlotte, North Carolina, 28262
Levine Cancer Institute-Ballantyne
Charlotte, North Carolina, 28277
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Jefferson Cherry Hill Hospital
Cherry Hill, New Jersey, 08002
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Oncology Hematology Care Inc-Kenwood
Cincinnati, Ohio, 45236
Bethesda North Hospital
Cincinnati, Ohio, 45242
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015
Morton Plant Hospital
Clearwater, Florida, 33756
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012
MetroHealth Medical Center
Cleveland, Ohio, 44109
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado, 80907
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Saint Francis Cancer Center
Colorado Springs, Colorado, 80923
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Memorial Sloan Kettering Commack
Commack, New York, 11725
New Hampshire Oncology Hematology PA-Concord
Concord, New Hampshire, 03301
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
MD Anderson in The Woodlands
Conroe, Texas, 77384
Mercy Hospital
Coon Rapids, Minnesota, 55433
Bay Area Hospital
Coos Bay, Oregon, 97420
Baptist Health Corbin
Corbin, Kentucky, 40701
Ochsner Hematology Oncology North Shore - Covington (West Region)
Covington, Louisiana, 70433
Greater Regional Medical Center
Creston, Iowa, 50801
Northwest Cancer Center - Main Campus
Crown Point, Indiana, 46307
AMG Crystal Lake - Oncology
Crystal Lake, Illinois, 60014
UPMC Western Maryland
Cumberland, Maryland, 21502
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Carle at The Riverfront
Danville, Illinois, 61832
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
Emory Decatur Hospital
Decatur, Georgia, 30033
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
UCHealth - Cherry Creek
Denver, Colorado, 80206
AdventHealth Porter
Denver, Colorado, 80210
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado, 80218
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Henry Ford Hospital
Detroit, Michigan, 48202
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Essentia Health Saint Mary's - Detroit Lakes Clinic
Detroit Lakes, Minnesota, 56501
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Advocate Good Samaritan Hospital
Downers Grove, Illinois, 60515
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805
Miller-Dwan Hospital
Duluth, Minnesota, 55805
Duke University Medical Center
Durham, North Carolina, 27710
Northwest Oncology LLC
Dyer, Indiana, 46311
Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Saint Elizabeth Healthcare Edgewood
Edgewood, Kentucky, 41017
Fairview Southdale Hospital
Edina, Minnesota, 55435
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Advocate Sherman Hospital
Elgin, Illinois, 60123
Mercy Cancer Center - Elk Grove
Elk Grove, California, 95758
Elmhurst Memorial Hospital
Elmhurst, Illinois, 60126
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505
Saint Vincent Hospital
Erie, Pennsylvania, 16544
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Providence Regional Cancer Partnership
Everett, Washington, 98201
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Farmington Health Center
Farmington, Utah, 84025
Corewell Health Farmington Hills Hospital
Farmington Hills, Michigan, 48336
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121
Armes Family Cancer Center
Findlay, Ohio, 45840
Blanchard Valley Hospital
Findlay, Ohio, 45840
Orion Cancer Care
Findlay, Ohio, 45840
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
The New York Hospital Medical Center of Queens
Flushing, New York, 11355
Levine Cancer Institute - Rutherford
Forest City, North Carolina, 28043
Northwell Health Physicians Partners Radiation Medicine at Queens
Forest Hills, New York, 11375
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903
Saint Elizabeth Healthcare Fort Thomas
Fort Thomas, Kentucky, 41075
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
Tarrant County Hospital District/JPS Health Network
Fort Worth, Texas, 76104
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
Essentia Health - Fosston
Fosston, Minnesota, 56542
Dana-Farber Cancer Institute at Foxborough
Foxborough, Massachusetts, 02035
Dayton Physicians LLC-Atrium
Franklin, Ohio, 45005
Washington Hospital
Fremont, California, 94538
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Gibbs Cancer Center-Gaffney
Gaffney, South Carolina, 29341
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Western Illinois Cancer Treatment Center
Galesburg, Illinois, 61401
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846
Levine Cancer Institute-Gaston
Gastonia, North Carolina, 28054
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Tidelands Georgetown Memorial Hospital
Georgetown, South Carolina, 29440
The West Clinic - Wolf River
Germantown, Tennessee, 38138
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022
Glens Falls Hospital
Glens Falls, New York, 12801
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Lutheran Hospital - Cancer Centers of Colorado
Golden, Colorado, 80401
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Northwell Health Cancer Institute at Huntington
Greenlawn, New York, 11740
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601
East Carolina University
Greenville, North Carolina, 27834
Dayton Physicians LLC-Wayne
Greenville, Ohio, 45331
Wayne Hospital
Greenville, Ohio, 45331
UPMC Hillman Cancer Center in Greenville/UPMC Horizon
Greenville, Pennsylvania, 16125
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
Henry Ford Saint John Hospital - Van Elslander
Grosse Pointe Woods, Michigan, 48236
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Hartford Hospital
Hartford, Connecticut, 06102
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Hi-Line Sletten Cancer Center
Havre, Montana, 59501
Essentia Health-Hayward Clinic
Hayward, Wisconsin, 54843
Advocate South Suburban Hospital
Hazel Crest, Illinois, 60429
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada, 89052
OptumCare Cancer Care at Seven Hills
Henderson, Nevada, 89052
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
Hayworth Cancer Center
High Point, North Carolina, 27262
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, 80129
University of North Carolina-Hillsborough Campus
Hillsborough, North Carolina, 27278
Northwest Cancer Center - Hobart
Hobart, Indiana, 46342
Saint Mary Medical Center
Hobart, Indiana, 46342
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Kuakini Medical Center
Honolulu, Hawaii, 96817
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Ben Taub General Hospital
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
IRMC Cancer Center
Indiana, Pennsylvania, 15701
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
City of Hope at Irvine Lennar
Irvine, California, 92618
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Allegiance Health
Jackson, Michigan, 49201
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Essentia Health - Jamestown Clinic
Jamestown, North Dakota, 58401
MU Health Care Goldschmidt Cancer Center
Jefferson City, Missouri, 65109
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Emory Johns Creek Hospital
Johns Creek, Georgia, 30097
Puerto Rico6 sites
Cancer Center-Metro Medical Center Bayamon
Bayamón, 00959-5060
Doctors Cancer Center
Manati, 00674
Pan American Center for Oncology Trials LLC
San Juan, 00902
San Juan Community Oncology Group
San Juan, 00917
Centro Comprensivo de Cancer de UPR
San Juan, 00927
San Juan City Hospital
San Juan, 00936
About this study
Official title: The Janus Rectal Cancer Trial: A Randomized Phase II/III Trial Testing the Efficacy of Triplet Versus Doublet Chemotherapy Regarding Clinical Complete Response and Disease-free Survival in Patients With Locally Advanced Rectal Cancer
This phase II/III trial compares the effect of usual treatment approach alone (FOLFOX or CAPOX after chemoradiation) with using FOLFIRINOX after chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy regimens, such as FOLFIRINOX (folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, and oxaliplatin), or CAPOX (capecitabine and oxaliplatin) use more than one anticancer drug that work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate for the primary rectal tumor and lead to higher rates of clinical complete response (and thus a chance to avoid surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate and compare the clinical complete response (cCR) rates in patients with locally advanced rectal cancer treated with neoadjuvant long-course radiotherapy (LCRT) followed by neoadjuvant modified leucovorin fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) versus neoadjuvant LCRT followed by neoadjuvant modified leucovorin , fluorouracil, and oxaliplatin (mFOLFOX6)/CAPOX (Phase II).
II. To evaluate and compare disease-free survival (DFS) in patients with locally advanced rectal cancer treated with neoadjuvant LCRT followed by neoadjuvant mFOLFIRINOX versus neoadjuvant LCRT followed by neoadjuvant mFOLFOX6/CAPOX. (Phase III)
SECONDARY OBJECTIVES:
- To evaluate and compare organ-preservation-time (OPT) between two treatment arms.
II. To evaluate and compare time to distant metastasis between two treatment arms.
III. To evaluate and compare overall survival (OS) between two treatment arms. IV. To evaluate and compare toxicity profiles of total neoadjuvant therapy (TNT) between two treatment arms.
- To evaluate and compare sustained cCR between two treatment arms.
EXPLORATORY OBJECTIVE:
- Evaluation of circulating tumor deoxyribonucleic acid (ctDNA) kinetics during neoadjuvant therapy \& surveillance and to correlate with radiographic, pathologic, and clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I:
LCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive either FOLFOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV bolus over 2-4 minutes and IV continuous infusion over 46-48 hours on day 1 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle or CAPOX consisting of capecitabine orally on days 1-14 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle. Treatment with FOLFOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Treatment with CAPOX repeats every 3 weeks for up to 5 cycles (15 weeks) in the absence of disease progression or unacceptable toxicity.
ARM II:
LCRT: Patients undergo long course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive FOLFIRINOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle, oxaliplatin IV over 2 hours on day 1 of each cycle, and irinotecan IV over 30-90 minutes on day 1 of each cycle) Treatment with FOLFIRINOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity.
All patients undergo CT scan, MRI scan, and collection of blood samples, and sigmoidoscopy throughout the trial and undergo biopsy during screening.
- Conditions
- Stage II Rectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Locally Advanced Rectal Adenocarcinoma
- Being tested
- Capecitabine, 5-fluorouracil, Leucovorin calcium, Irinotecan, Oxaliplatin
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Given PO
5-fluorouracilDrug
Given IV
Given IV
IrinotecanDrug
Given IV
OxaliplatinDrug
Given IV
Long Course ChemoradiotherapyRadiation
Receive LCRT
Computed TomographyProcedure or surgery
undergo CT
Magnetic Resonance ImagingProcedure or surgery
undergo MRI
SigmoidoscopyProcedure or surgery
undergo sigmoidoscopy
biopsyProcedure or surgery
undergo biopsy
| Study group | Role | What they receive |
|---|---|---|
| Arm I (LCRT, FOLFOX or CAPOX) | Active comparator | LCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. Consolidation: Patients receive either: FOLFOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV bolus over 2-4 minutes and IV continuous infusion over 46-48 hours on day 1 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle) or CAPOX (consisting of capecitabine PO on days 1-14 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle). Treatment with FOLFOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Treatment with CAPOX repeats every 3 weeks for up to 5 cycles (15 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, collection of blood samples and sigmoidoscopy throughout the trial and undergo biopsy during screening. Receives: Drug: Capecitabine; Drug: 5-fluorouracil; Drug: Leucovorin calcium; Drug: Oxaliplatin; Radiation: Long Course Chemoradiotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Sigmoidoscopy; Procedure: biopsy |
| Arm II (LCRT, FOLFIRINOX) | Experimental | LCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive FOLFIRINOX (consisting of leucovorin over 2 hours on day 1 of each cycle, fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle, oxaliplatin IV over 2 hours on day 1 of each cycle, and irinotecan IV over 30-90 minutes on day 1 of each cycle). Treatment with FOLFIRINOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and collection of blood samples and sigmoidoscopy throughout the trial and undergo biopsy during screening. Receives: Drug: Capecitabine; Drug: 5-fluorouracil; Drug: Leucovorin calcium; Drug: Irinotecan; Drug: Oxaliplatin; Radiation: Long Course Chemoradiotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Sigmoidoscopy; Procedure: biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clincal Complete Response (cCR) Rates (Phase II)
Defined as the number of patients who achieved cCR at the end of total neoadjuvant therapy (TNT) divided by number of patients included in the analysis population. This endpoint will be assessed within 8-12 weeks after completion of TNT. If there is a cCR, then the patient will be counted in the numerator. If there is a near-complete response (nCR) then a re-evaluation within 4-8 weeks will be performed. If an nCR evolved to a cCR, then the patient will be counted in the numerator. Otherwise, the patient will be deemed as NOT achieving cCR status. Difference of proportions test will be conducted to compare cCR rate in the experimental arm to cCR rate in the control arm. If the one-sided p-value of the comparison is < 0.05 (difference in proportion > 9.3%), then we will conclude the cCR rate in the experimental arm is superior to the control arm.
Measured: Up to 5 years
Disease-free survival (DFS) rate (Phase III)
Defined as the time from date of randomization to the date of first occurrence of the following events: death due to all causes, tumor that recurs locally after an R0 total mesorectal excision (TME), tumor that regrows after an initial apparent clinical and radiological CR and cannot be surgically removed with an R0 TME, and M1 disease diagnosed at any point after the initiation of treatment. Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.
Measured: From date of randomization, assessed up to 5 years
Secondary outcomes (5)
Organ-preservation time (OPT)
Defined as time from the date of randomization to the date of the first occurrence of the following events: TME performed or attempted, tumor that regrows after an initial apparent clinical and radiological complete response (CR) and death due to all causes. Will be estimated, in each arm, using the method of Kaplan-Meier and treatment compared by a stratified Cox regression model.
Measured: From date of randomization, assessed up to 5 years
Time to distant metastasis (TDM)
Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.
Measured: From the date of randomization to the date of first documented distant metastasis, assessed up to 5 years
Overall survival (OS)
Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.
Measured: From the date of randomization to the date of death due to all causes, assessed up to 5 years
Incidence of adverse events (AEs)
Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of each type of AE. The overall adverse event rates for grade 3 or higher adverse events will be compared between two treatment groups using Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).
Measured: Up to 5 years
Sustained cCR
Defined as a binary endpoint with two statuses: responder and non-responder. Responders are defined as those evaluable patients who achieved at least one of the following within 3 years after randomization:
- Had TME and the pathologic outcome is pathologic complete response
- Had a cCR, were on watch and wait (WW) with no regrowth and no distant metastases
- Had nCR, were on WW with no regrowth and no distant metastases Non-responders are defined as all patients who did not meet the criteria as noted above for the responders.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2022
- Study start8 Dec 2022
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jul 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Stage II Rectal Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 760 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- J. Joshua Smith, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05610163
- Sponsor's protocol ID
- A022104
- Other IDs
- U10CA180821, NCI-2022-07800, NRG-GI010
- Acronym
- JANUS
- Status last verified
- Sep 2026
- First submitted
- 1 Nov 2022
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Raman S, Khalil MA, Eisenstein S, Lin M. Selected Abstracts. Dis Colon Rectum. 2026 Jul 1;69(7):1938-1942. doi: 10.1097/DCR.0000000000004250. Epub 2026 Apr 7. No abstract available.
PubMed 42328901Scott AJ, Kennedy EB, Berlin J, Brown G, Chalabi M, Cho MT, Cusnir M, Dorth J, George M, Kachnic LA, Kennecke HF, Loree JM, Morris VK, Perez RO, Smith JJ, Strickland MR, Gholami S. Management of Locally Advanced Rectal Cancer: ASCO Guideline. J Clin Oncol. 2024 Oct;42(28):3355-3375. doi: 10.1200/JCO.24.01160. Epub 2024 Aug 8.
PubMed 39116386Alvarez JA, Shi Q, Dasari A, Garcia-Aguilar J, Sanoff H, George TJ, Hong T, Yothers G, Philip P, Nelson G, Al Baghdadi T, Alese OB, Zambare W, Omer D, Verheij FS, Bercz A, Kim MJ, Buckley J, Williams H, George M, Garcia R, Gallagher P, O'Reilly EM, Meyerhardt JA, Crawley J, Shergill A, Horvat N, Romesser PB, Hall W, Smith JJ. Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer. BMC Cancer. 2024 Jul 26;24(1):901. doi: 10.1186/s12885-024-12529-7.
PubMed 39060961Alvarez J, Shi Q, Dasari A, Garcia-Aguilar J, Sanoff H, George TJ, Hong TS, Yothers G, Philip PA, Nelson GD, Al Baghdadi T, Alese O, Zambare W, Omer DM, Verheij FS, Buckley J, Williams H, George M, Garcia R, O'Reilly EM, Meyerhardt JA, Shergill A, Horvat N, Romesser PB, Hall WA, Smith JJ. ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer. medRxiv [Preprint]. 2024 Apr 27:2024.04.25.24306396. doi: 10.1101/2024.04.25.24306396.
PubMed 38712176Langenfeld SJ, Davis BR, Vogel JD, Davids JS, Temple LKF, Cologne KG, Hendren S, Hunt S, Garcia Aguilar J, Feingold DL, Lightner AL, Paquette IM; Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer 2023 Supplement. Dis Colon Rectum. 2024 Jan 1;67(1):18-31. doi: 10.1097/DCR.0000000000003057. Epub 2023 Aug 20. No abstract available.
PubMed 37647138
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Janus Rectal Cancer Trial: A Randomized Phase II/III Trial Testing the Efficacy of Triplet Versus Doublet Chemotherapy Regarding Clinical Complete Response and Disease-free Survival in Patients With Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT05610163
- Acronym / sponsor ID
- JANUS / A022104
- Conditions
- Stage II Rectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Locally Advanced Rectal Adenocarcinoma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 760 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Dec 2022 (actual)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 1 Jul 2037 (estimated)
- First posted
- 9 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II/III trial compares the effect of usual treatment approach alone (FOLFOX or CAPOX after chemoradiation) with using FOLFIRINOX after chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy regimens, such as FOLFIRINOX (folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, and oxaliplatin), or CAPOX (capecitabine and oxaliplatin) use more than one anticancer drug that work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate for the primary rectal tumor and lead to higher rates of clinical complete response (and thus a chance to avoid surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate and compare the clinical complete response (cCR) rates in patients with locally advanced rectal cancer treated with neoadjuvant long-course radiotherapy (LCRT) followed by neoadjuvant modified leucovorin fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) versus neoadjuvant LCRT followed by neoadjuvant modified leucovorin , fluorouracil, and oxaliplatin (mFOLFOX6)/CAPOX (Phase II).
II. To evaluate and compare disease-free survival (DFS) in patients with locally advanced rectal cancer treated with neoadjuvant LCRT followed by neoadjuvant mFOLFIRINOX versus neoadjuvant LCRT followed by neoadjuvant mFOLFOX6/CAPOX. (Phase III)
SECONDARY OBJECTIVES:
- To evaluate and compare organ-preservation-time (OPT) between two treatment arms.
II. To evaluate and compare time to distant metastasis between two treatment arms.
III. To evaluate and compare overall survival (OS) between two treatment arms. IV. To evaluate and compare toxicity profiles of total neoadjuvant therapy (TNT) between two treatment arms.
- To evaluate and compare sustained cCR between two treatment arms.
EXPLORATORY OBJECTIVE:
- Evaluation of circulating tumor deoxyribonucleic acid (ctDNA) kinetics during neoadjuvant therapy \& surveillance and to correlate with radiographic, pathologic, and clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I:
LCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive either FOLFOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV bolus over 2-4 minutes and IV continuous infusion over 46-48 hours on day 1 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle or CAPOX consisting of capecitabine orally on days 1-14 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle. Treatment with FOLFOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Treatment with CAPOX repeats every 3 weeks for up to 5 cycles (15 weeks) in the absence of disease progression or unacceptable toxicity.
ARM II:
LCRT: Patients undergo long course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive FOLFIRINOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle, oxaliplatin IV over 2 hours on day 1 of each cycle, and irinotecan IV over 30-90 minutes on day 1 of each cycle) Treatment with FOLFIRINOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity.
All patients undergo CT scan, MRI scan, and collection of blood samples, and sigmoidoscopy throughout the trial and undergo biopsy during screening.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (LCRT, FOLFOX or CAPOX) | Active comparator | Drug: Capecitabine, Drug: 5-fluorouracil, Drug: Leucovorin calcium, Drug: Oxaliplatin, Radiation: Long Course Chemoradiotherapy, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Sigmoidoscopy, Procedure: biopsyLCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. Consolidation: Patients receive either: FOLFOX (consisting of leucovorin IV over 2 hours on day 1 of each cycle, fluorouracil IV bolus over 2-4 minutes and IV continuous infusion over 46-48 hours on day 1 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle) or CAPOX (consisting of capecitabine PO on days 1-14 of each cycle, and oxaliplatin IV over 2 hours on day 1 of each cycle). Treatment with FOLFOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Treatment with CAPOX repeats every 3 weeks for up to 5 cycles (15 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, collection of blood samples and sigmoidoscopy throughout the trial and undergo biopsy during screening. |
| Arm II (LCRT, FOLFIRINOX) | Experimental | Drug: Capecitabine, Drug: 5-fluorouracil, Drug: Leucovorin calcium, Drug: Irinotecan, Drug: Oxaliplatin, Radiation: Long Course Chemoradiotherapy, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Sigmoidoscopy, Procedure: biopsyLCRT: Patients undergo long-course chemoradiation therapy for up to 5 weeks. CONSOLIDATION: Patients receive FOLFIRINOX (consisting of leucovorin over 2 hours on day 1 of each cycle, fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle, oxaliplatin IV over 2 hours on day 1 of each cycle, and irinotecan IV over 30-90 minutes on day 1 of each cycle). Treatment with FOLFIRINOX repeats every 2 weeks for up to 8 cycles (16 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and collection of blood samples and sigmoidoscopy throughout the trial and undergo biopsy during screening. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologic Documentation: rectal adenocarcinoma, mismatch repair proficient (pMMR)
- Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection (APR) or coloanal anastomosis
- Tumor site: Rectum; distal edge of the tumor =< 12cm from the anal verge (as determined by surgeon's endoscopic assessment; MRI can be used to compliment this information, but endoscopy should be the primary means of assessment)
- No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer within the past 5 years is allowed. No local approaches to excising the rectal cancer (even if done for diagnostic purposes) are allowed (e.g., transanal excision [open or minimally invasive], local excision, endoscopic submucosal dissection or endoscopic submucosal resection).
- Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineGiven PO | Drug | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| 5-fluorouracilGiven IV | Drug | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| Leucovorin calciumGiven IV | Drug | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| IrinotecanGiven IV | Drug | Arm II (LCRT, FOLFIRINOX) |
| OxaliplatinGiven IV | Drug | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| Long Course ChemoradiotherapyReceive LCRT | Radiation | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| Computed Tomographyundergo CT | Procedure or surgery | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| Magnetic Resonance Imagingundergo MRI | Procedure or surgery | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| Sigmoidoscopyundergo sigmoidoscopy | Procedure or surgery | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
| biopsyundergo biopsy | Procedure or surgery | Arm I (LCRT, FOLFOX or CAPOX), Arm II (LCRT, FOLFIRINOX) |
Primary outcome
Clincal Complete Response (cCR) Rates (Phase II)
Time frame: Up to 5 years
Defined as the number of patients who achieved cCR at the end of total neoadjuvant therapy (TNT) divided by number of patients included in the analysis population. This endpoint will be assessed within 8-12 weeks after completion of TNT. If there is a cCR, then the patient will be counted in the numerator. If there is a near-complete response (nCR) then a re-evaluation within 4-8 weeks will be performed. If an nCR evolved to a cCR, then the patient will be counted in the numerator. Otherwise, the patient will be deemed as NOT achieving cCR status. Difference of proportions test will be conducted to compare cCR rate in the experimental arm to cCR rate in the control arm. If the one-sided p-value of the comparison is < 0.05 (difference in proportion > 9.3%), then we will conclude the cCR rate in the experimental arm is superior to the control arm.
Disease-free survival (DFS) rate (Phase III)
Time frame: From date of randomization, assessed up to 5 years
Defined as the time from date of randomization to the date of first occurrence of the following events: death due to all causes, tumor that recurs locally after an R0 total mesorectal excision (TME), tumor that regrows after an initial apparent clinical and radiological CR and cannot be surgically removed with an R0 TME, and M1 disease diagnosed at any point after the initiation of treatment. Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.
5 secondary outcomes
Organ-preservation time (OPT)
Time frame: From date of randomization, assessed up to 5 years
Time to distant metastasis (TDM)
Time frame: From the date of randomization to the date of first documented distant metastasis, assessed up to 5 years
Overall survival (OS)
Time frame: From the date of randomization to the date of death due to all causes, assessed up to 5 years
Incidence of adverse events (AEs)
Time frame: Up to 5 years
Sustained cCR
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Derived from this study: PubMed 42328901Raman S, Khalil MA, Eisenstein S, Lin M. Selected Abstracts. Dis Colon Rectum. 2026 Jul 1;69(7):1938-1942. doi: 10.1097/DCR.0000000000004250. Epub 2026 Apr 7. No abstract available.
- Derived from this study: PubMed 39116386Scott AJ, Kennedy EB, Berlin J, Brown G, Chalabi M, Cho MT, Cusnir M, Dorth J, George M, Kachnic LA, Kennecke HF, Loree JM, Morris VK, Perez RO, Smith JJ, Strickland MR, Gholami S. Management of Locally Advanced Rectal Cancer: ASCO Guideline. J Clin Oncol. 2024 Oct;42(28):3355-3375. doi: 10.1200/JCO.24.01160. Epub 2024 Aug 8.
- Derived from this study: PubMed 39060961Alvarez JA, Shi Q, Dasari A, Garcia-Aguilar J, Sanoff H, George TJ, Hong T, Yothers G, Philip P, Nelson G, Al Baghdadi T, Alese OB, Zambare W, Omer D, Verheij FS, Bercz A, Kim MJ, Buckley J, Williams H, George M, Garcia R, Gallagher P, O'Reilly EM, Meyerhardt JA, Crawley J, Shergill A, Horvat N, Romesser PB, Hall W, Smith JJ. Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer. BMC Cancer. 2024 Jul 26;24(1):901. doi: 10.1186/s12885-024-12529-7.
- Derived from this study: PubMed 38712176Alvarez J, Shi Q, Dasari A, Garcia-Aguilar J, Sanoff H, George TJ, Hong TS, Yothers G, Philip PA, Nelson GD, Al Baghdadi T, Alese O, Zambare W, Omer DM, Verheij FS, Buckley J, Williams H, George M, Garcia R, O'Reilly EM, Meyerhardt JA, Shergill A, Horvat N, Romesser PB, Hall WA, Smith JJ. ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer. medRxiv [Preprint]. 2024 Apr 27:2024.04.25.24306396. doi: 10.1101/2024.04.25.24306396.
- Derived from this study: PubMed 37647138Langenfeld SJ, Davis BR, Vogel JD, Davids JS, Temple LKF, Cologne KG, Hendren S, Hunt S, Garcia Aguilar J, Feingold DL, Lightner AL, Paquette IM; Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer 2023 Supplement. Dis Colon Rectum. 2024 Jan 1;67(1):18-31. doi: 10.1097/DCR.0000000000003057. Epub 2023 Aug 20. No abstract available.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. Joshua Smith, MD study chair
Memorial Sloan Kettering Cancer Center
685 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Capecitabine, 5-fluorouracil and Leucovorin calcium in people with Stage II Rectal Cancer AJCC v8 and Stage III Rectal Cancer AJCC v8, run by Alliance for Clinical Trials in Oncology at 685 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 685 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clincal Complete Response (cCR) Rates (Phase II) (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05610163, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.