Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Phase III Trial of Perioperative Versus Adjuvant Chemotherapy for Resectable Pancreatic Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04340141
• Other study ID #: A021806
• Secondary ID: NCI-2020-01560U1
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2020
• Est. completion date: November 2030

Study information

• Verified date: April 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Cristina R. Ferrone, MD
• Phone: 617-643-6189
• Email: cferrone[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares perioperative chemotherapy (given before and after surgery) versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, and oxaliplatin, 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. Giving chemotherapy before and after surgery (perioperatively) may work better in treating patients with pancreatic cancer compared to giving chemotherapy after surgery (adjuvantly).

Description:

PRIMARY OBJECTIVES: I. To evaluate and compare overall survival (OS) in patients with resectable pancreatic adenocarcinoma treated with perioperative fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (modified [m]FOLFIRINOX) and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. II. To evaluate and compare time to locoregional recurrence (TLR) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. III. To evaluate and compare time to distant metastases (TDM) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. IV. To evaluate and compare the R0 resection rate in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. V. To evaluate and compare rate of unresectability in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. VI. To evaluate rate of pathologic complete response in patients randomized to the perioperative therapy arm. VII. To evaluate and compare mFOLFIRINOX dose intensity delivered and number of cycles received in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. VIII. To evaluate and compare adverse event profile in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. IX. To compare physical functioning, nausea/vomiting, and diarrhea, as measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) between patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX. X. To prospectively assess the influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on the disease-free survival and overall survival among patients with localized pancreatic cancers. XI. To assess the influence of diet, obesity, physical activity, and other lifestyle habits on the risk of toxicity associated with chemotherapy. XII. To evaluate the ability of computed tomography (CT)-based radiomics in distinguishing post-neoadjuvant chemotherapy (NAC) fibrosis from viable tumor in patients randomized to the perioperative therapy arm. XIII. To determine whether CT-based radiomics retrieved from baseline examination may act as non-invasive predictors of survival outcome in patients randomized to the adjuvant therapy arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 352
• Est. completion date: November 2030
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

PRE-REGISTRATION:

• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
• Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance

imaging (MRI) scan and 2) chest CT:

• No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
• No evidence of metastatic disease
• Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging

REGISTRATION:

• Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
• 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 done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Total Neuropathy Score < 2
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelet count >= 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
• Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
• No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
• No comorbid conditions that would prohibit curative-intent pancreatectomy
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration

Related Conditions & MeSH terms

• Carcinoma, Adenosquamous
• Pancreatic Adenosquamous Carcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Resectable Pancreatic Adenocarcinoma

Intervention

Drug:
• Oxaliplatin
Given IV
• Irinotecan Hydrochloride
Given IV
• Leucovorin Calcium
Given IV
• Fluorouracil
Given IV

Procedure:
• Resection
Undergo surgical resection

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA-Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Augusta University Medical Center	Augusta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	South Shore University Hospital	Bay Shore	New York
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Community Cancer Institute	Clovis	California
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Northshore Oncology Associates-Covington	Covington	Louisiana
United States	Ochsner Hematology Oncology North Shore - Covington (West Region)	Covington	Louisiana
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danbury Hospital	Danbury	Connecticut
United States	Carle at The Riverfront	Danville	Illinois
United States	Miami Valley Hospital	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Kaiser Permanente Dublin	Dublin	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Cancer Institute at Saint Francis Hospital	East Hills	New York
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Thomas Hospital	Fairhope	Alabama
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Smilow Cancer Hospital Care Center at Glastonbury	Glastonbury	Connecticut
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Northwell Health Cancer Institute at Huntington	Greenlawn	New York
United States	East Carolina University	Greenville	North Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Smilow Cancer Hospital Care Center at Greenwich	Greenwich	Connecticut
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	Jersey City Medical Center	Jersey City	New Jersey
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Baptist Health Madisonville/Merle Mahr Cancer Center	Madisonville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Midstate Medical Center	Meriden	Connecticut
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	CarolinaEast Medical Center	New Bern	North Carolina
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai West	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Sentara Leigh Hospital	Norfolk	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Northwestern Medicine Orland Park	Orland Park	Illinois
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	AdventHealth Orlando	Orlando	Florida
United States	Upstate Cancer Center at Oswego	Oswego	New York
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Queens Cancer Center	Rego Park	New York
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Hospital	Ridgewood	New Jersey
United States	University of Rochester	Rochester	New York
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Mills Health Center	San Mateo	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Staten Island University Hospital	Staten Island	New York
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	SUNY Upstate Medical Center-Community Campus	Syracuse	New York
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	UM Saint Joseph Medical Center	Towson	Maryland
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Upstate Cancer Center at Verona	Verona	New York
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Wilmot Cancer Institute at Webster	Webster	New York
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Smilow Cancer Hospital Care Center - Westerly	Westerly	Rhode Island
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Overall survival is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. The treatment arms will be compared using a stratified Cox regression model, and hazard ratios from each arm will be estimated.	Time between randomization and death from any cause, assessed up to 6 years.
Secondary	Disease-free survival (DFS)	Disease-free survival (DFS) is defined as the time from randomization to the date of progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, whichever occurs first. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	Time between randomization and progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, assessed up to 6 years.
Secondary	Time to locoregional recurrence (TLR)	Time to locoregional recurrence (TLR) is defined as the time from randomization to the date of locoregional recurrence after resection. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	Time between randomization and locoregional recurrence after resection, assessed up to 6 years.
Secondary	Time to distant metastases (TDM)	Time to distant metastases (TDM) is defined as the time from randomization to the date of metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	Time between randomization and metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection, assessed up to 6 years.
Secondary	R0 resection rate	The rate (percentage) of patients with negative resection margins after undergoing surgery.	At time of surgery.
Secondary	Rate of unresectability	The rate (percentage) of patients who cannot undergo surgery due to adverse events, progressive disease, death, poor performance, or patient/physician decision, are deemed unresectable before surgery, or resection was not performed during surgery.	At time of surgery or planned time of surgery.
Secondary	Pathologic complete response (pCR) rate	The rate (percentage) of patients who achieve a pathologic complete response (pCR) confirmed by histopathologic review of the surgical specimen.	At time of surgery.
Secondary	Incidence of adverse events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0)	The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns within treatment arms and during the following three time points: during perioperative chemotherapy, surgical complications during surgery and post-operative period for 30 days, and during adjuvant chemotherapy.	Up to 2 years.
Secondary	Fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (modified [m]FOLFIRINOX) dose intensity delivered	Dose intensity is defined as the percentage of total cumulative dose the patient received divided by the total dose planned per protocol times 100.	8 months
Secondary	Fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (modified [m]FOLFIRINOX) number of cycles received	The number of cycles received is defined as the total number of cycles that the participant received at least one dose of any agent in mFOLFIRINOX.	8 months
Secondary	Quality of life as assessed by the physical functioning, nausea/vomiting, and diarrhea subscales in the Quality of Life Questionnaire-Core 30 (QLQ-C30)	Quality of Life Questionnaire-Core 30 (QLQ-C30) is a 30-item questionnaire to assess the overall quality of life in cancer patients. QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning, greater occurrence of nausea/vomiting, and greater occurrence of diarrhea.	8 weeks
Secondary	Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on overall survival	Multivariate Cox proportional hazards models will be fit for overall survival (OS) endpoint (defined above) with covariates corresponding to baseline diet and lifestyle questionnaire responses and hazard ratios and 95% confidence intervals will be reported.	Time between randomization and death from any cause, assessed up to 6 years.
Secondary	Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on disease-free survival (DFS)	Multivariate Cox proportional hazards models will be fit for disease-free survival (DFS) endpoint (defined above) with covariates corresponding to baseline diet and lifestyle questionnaire responses and hazard ratios and 95% confidence intervals will be reported.	Time between randomization and progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, assessed up to 6 years.
Secondary	Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on the risk of grade 3+ adverse event associated with chemotherapy	Multivariate Logistic models will be fit for the binary endpoint of grade 3+ adverse event (patient experiences at least one grade 3 or higher adverse event during treatment)	Up to 2 years.
Secondary	The ability of computed tomography (CT)-based radiomics to distinguish post-neoadjuvant chemotherapy (NAC) fibrosis from viable tumor as measured by comparison to histological evaluation	Comparison between computed tomography (CT)-based radiomics and histological tumor fibrosis proportions will be measured using Spearman's rank correlation coefficient.	At time of surgery.
Secondary	Computed tomography (CT)-based radiomics as non-invasive predictors of overall survival	Multivariate Cox proportional hazards model will be fit for overall survival (OS) endpoint (defined above) with covariates chosen from all available radiomics features using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation (CV) and additionally adjusted for clinically important confounders. After the final model is selected the area under the receiver operating characteristic curve (AUC) will be reported to indicate the prediction performance of the radiomics model.	Time between randomization and death from any cause, assessed up to 6 years.