Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer

NCT ID: NCT02839343

Last Updated: 2022-05-24

Study Results

Results available

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Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Brief Summary

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This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, 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. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.

Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy.

SECONDARY OBJECTIVES:

I. To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens.

II. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens.

III. To evaluate and estimate the pathologic compete response (pCR) rates in patients receiving each of the two multimodality treatment regimens.

IV. To assess the adverse events (AE) profile and safety of each treatment arm.

TERTIARY OBJECTIVES:

I. To test the effect of the rs2853564 vitamin D receptor (VDR) variant on OS rate and discover novel candidate genes associated with OS and severe toxicity of chemotherapy by using genome-wide genotyping approaches.

II. To evaluate risk classification previously developed by Koay et al using normalized area under the enhancement curve (NAUC).

III. To access prognostic value of NAUC ratio defined as post-neoadjuvant NAUC divided by pre-neoadjuvant therapy NAUC.

IV. To evaluate risk classification previously developed by Koay et al using delta measure.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive either stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT) on days 1-5 of course 8.

SURGERY Within 4 to 8 weeks after the last dose of chemotherapy (arm A) or of radiation (arm B), patients considered surgical candidates for resection (after central review) will undergo surgery at the registering institution.

ADJUVANT CHEMOTHERAPY Within 4-12 weeks from the date of surgery, patients will receive oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 16 weeks for 2 years, then every 6 months for 5 years.

Conditions

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Pancreatic Adenocarcinoma Borderline Resectable Adenocarcinoma of the Head of the Pancrease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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mFOLFIRINOX + surgery + FOLFOX

Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.

Group Type EXPERIMENTAL

surgery

Intervention Type PROCEDURE

mFOLFIRINOX

Intervention Type DRUG

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV

FOLFOX

Intervention Type DRUG

oxaliplatin IV, leucovorin IV and 5-FU IV

mFOLFIRINOX + radiation + surgery + FOLFOX

Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.

Group Type EXPERIMENTAL

radiation therapy

Intervention Type RADIATION

surgery

Intervention Type PROCEDURE

mFOLFIRINOX

Intervention Type DRUG

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV

FOLFOX

Intervention Type DRUG

oxaliplatin IV, leucovorin IV and 5-FU IV

Interventions

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radiation therapy

Intervention Type RADIATION

surgery

Intervention Type PROCEDURE

mFOLFIRINOX

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV

Intervention Type DRUG

FOLFOX

oxaliplatin IV, leucovorin IV and 5-FU IV

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
* No prior chemotherapy or radiation for pancreatic cancer
* No definitive resection of pancreatic cancer
* Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (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
* No grade \>= 2 neuropathy
* No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration
* Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 x upper limit of normal (ULN) or
* Calculated (calc.) creatinine clearance \> 45 mL/min
* Total bilirubin =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal (ULN)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Sky Foundation

OTHER

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew Katz, MD, FACS

Role: STUDY_CHAIR

The University of Texas MD Anderson Cancer Center

Locations

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Southern Cancer Center PC-Mobile

Mobile, Alabama, United States

Site Status

Southern Cancer Center PC-Springhill

Mobile, Alabama, United States

Site Status

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Site Status

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

Site Status

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

Site Status

University Oncology Associates

Clovis, California, United States

Site Status

Kaiser Permanente-Fremont

Fremont, California, United States

Site Status

Kaiser Permanente-Fresno

Fresno, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Los Angeles County-USC Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Kaiser Permanente-Modesto

Modesto, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Kaiser Permanente-Redwood City

Redwood City, California, United States

Site Status

Kaiser Permanente-Richmond

Richmond, California, United States

Site Status

Kaiser Permanente-Roseville

Roseville, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Site Status

Kaiser Permanente - Sacramento

Sacramento, California, United States

Site Status

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Site Status

Kaiser Permanente-San Francisco

San Francisco, California, United States

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Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

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Kaiser Permanente San Leandro

San Leandro, California, United States

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Kaiser Permanente-San Rafael

San Rafael, California, United States

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Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

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Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

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Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Site Status

Kaiser Permanente-Stockton

Stockton, California, United States

Site Status

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, United States

Site Status

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Site Status

Kaiser Permanente-Vallejo

Vallejo, California, United States

Site Status

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Memorial Hospital West

Pembroke Pines, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northwest Community Hospital

Arlington Heights, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

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Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois, United States

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NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, United States

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Loyola University Medical Center

Maywood, Illinois, United States

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Edward Hospital/Cancer Center

Naperville, Illinois, United States

Site Status

Edward Hospital/Cancer Center?Plainfield

Plainfield, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status

Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

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Iowa Methodist Medical Center

Des Moines, Iowa, United States

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University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

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The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

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Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford

Biddeford, Maine, United States

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MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford

Sanford, Maine, United States

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Maine Medical Center- Scarborough Campus

Scarborough, Maine, United States

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Saint Agnes Hospital

Baltimore, Maryland, United States

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Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

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Boston Medical Center

Boston, Massachusetts, United States

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Dana-Farber Cancer Institute

Boston, Massachusetts, United States

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University of Massachusetts Medical School

Worcester, Massachusetts, United States

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Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

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University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

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Bronson Battle Creek

Battle Creek, Michigan, United States

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Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

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Henry Ford Hospital

Detroit, Michigan, United States

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Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

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West Michigan Cancer Center

Kalamazoo, Michigan, United States

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McLaren Cancer Institute-Macomb

Mount Clemens, Michigan, United States

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McLaren Cancer Institute-Northern Michigan

Petoskey, Michigan, United States

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Ascension Saint Mary's Hospital

Saginaw, Michigan, United States

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Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States

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Southeast Cancer Center

Cape Girardeau, Missouri, United States

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University of Missouri - Ellis Fischel

Columbia, Missouri, United States

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Missouri Baptist Medical Center

St Louis, Missouri, United States

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CHI Health Good Samaritan

Kearney, Nebraska, United States

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Renown Regional Medical Center

Reno, Nevada, United States

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Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

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Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

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Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

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Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

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Morristown Medical Center

Morristown, New Jersey, United States

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Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

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Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

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University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

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Memorial Sloan Kettering Commack

Commack, New York, United States

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Memorial Sloan Kettering Westchester

Harrison, New York, United States

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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

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NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

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State University of New York Upstate Medical University

Syracuse, New York, United States

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Memorial Sloan Kettering Nassau

Uniondale, New York, United States

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Atrium Health Stanly/LCI-Albemarle

Albemarle, North Carolina, United States

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Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

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UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

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Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

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Atrium Health Lincoln/LCI-Lincoln

Charlotte, North Carolina, United States

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Levine Cancer Institute-SouthPark

Charlotte, North Carolina, United States

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Atrium Health University City/LCI-University

Charlotte, North Carolina, United States

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Levine Cancer Institute-Mallard Creek

Charlotte, North Carolina, United States

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Levine Cancer Institute-Ballantyne

Charlotte, North Carolina, United States

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Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina, United States

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Duke University Medical Center

Durham, North Carolina, United States

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Atrium Health Union/LCI-Union

Monroe, North Carolina, United States

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Atrium Health Cleveland/LCI-Cleveland

Shelby, North Carolina, United States

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NHRMC Radiation Oncology - Supply

Supply, North Carolina, United States

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New Hanover Regional Medical Center/Zimmer Cancer Center

Wilmington, North Carolina, United States

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NHRMC Radiation Oncology - 16th Street

Wilmington, North Carolina, United States

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Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Sanford Broadway Medical Center

Fargo, North Dakota, United States

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Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

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Providence Saint Vincent Medical Center

Portland, Oregon, United States

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Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, United States

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Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Pottstown Hospital

Pottstown, Pennsylvania, United States

Site Status

Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Faris

Greenville, South Carolina, United States

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Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

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Levine Cancer Institute-Rock Hill

Rock Hill, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Seneca

Seneca, South Carolina, United States

Site Status

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

IMG Hematology Oncology 8501

Fairfax, Virginia, United States

Site Status

IMG Hematology Oncology 8505

Fairfax, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Edwards Comprehensive Cancer Center

Huntington, West Virginia, United States

Site Status

West Virginia University Healthcare

Morgantown, West Virginia, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States

Site Status

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Snyder RA, Zemla TJ, Shi Q, Segovia D, Ahmad SA, O'Reilly EM, Herman JM, Katz MHG. Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501). Ann Surg Oncol. 2024 Oct;31(10):7033-7042. doi: 10.1245/s10434-024-15670-6. Epub 2024 Jul 15.

Reference Type DERIVED
PMID: 39008208 (View on PubMed)

Katz MHG, Shi Q, Meyers J, Herman JM, Chuong M, Wolpin BM, Ahmad S, Marsh R, Schwartz L, Behr S, Frankel WL, Collisson E, Leenstra J, Williams TM, Vaccaro G, Venook A, Meyerhardt JA, O'Reilly EM. Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2022 Sep 1;8(9):1263-1270. doi: 10.1001/jamaoncol.2022.2319.

Reference Type DERIVED
PMID: 35834226 (View on PubMed)

Katz MHG, Ou FS, Herman JM, Ahmad SA, Wolpin B, Marsh R, Behr S, Shi Q, Chuong M, Schwartz LH, Frankel W, Collisson E, Koay EJ, Hubbard JM, Leenstra JL, Meyerhardt J, O'Reilly E; Alliance for Clinical Trials on Oncology. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017 Jul 27;17(1):505. doi: 10.1186/s12885-017-3441-z.

Reference Type DERIVED
PMID: 28750659 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2016-00456

Identifier Type: REGISTRY

Identifier Source: secondary_id

A021501

Identifier Type: -

Identifier Source: org_study_id

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