Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer
- Conditions
- Pancreatic AdenocarcinomaBorderline Resectable Adenocarcinoma of the Head of the Pancrease
- Interventions
- Procedure: surgeryRadiation: radiation therapyDrug: mFOLFIRINOXDrug: FOLFOX
- Registration Number
- NCT02839343
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 126
- 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)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description mFOLFIRINOX + surgery + FOLFOX surgery 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. mFOLFIRINOX + surgery + FOLFOX mFOLFIRINOX 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. mFOLFIRINOX + surgery + FOLFOX 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. mFOLFIRINOX + radiation + surgery + FOLFOX radiation therapy 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. mFOLFIRINOX + radiation + surgery + FOLFOX surgery 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. mFOLFIRINOX + radiation + surgery + FOLFOX mFOLFIRINOX 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. mFOLFIRINOX + radiation + surgery + FOLFOX 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Rate 18 months Defined as the percentage of patients who are alive at 18 months after randomization divided by the total number of evaluable patients in each arm. An evaluable patient is defined as any patient who signed informed consent, deemed eligible by central review and received any protocol-defined treatment. 95% confidence interval will be estimated based on standard method. Chi-squared test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare 18 month OS rates among treatment arms. OS within each arm will be summarized by Kaplan-Meier method. Median, 1-year and 2-year rates will be estimated based on Kaplan-Meier curves.
- Secondary Outcome Measures
Name Time Method Residual Tumor (R)0 Resection Rate 24 months Defined as the percentage of patients in whom an achieved R0 resection was achieved during surgery.
Event-free Survival 4 years and 7 months Defined as time from randomization to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) surgery with R2 resection, 3) recurrent disease following surgery, or 4) death due to any cause. Will be estimated using the method of Kaplan-Meier in each arm and compared between treatment groups using the log-rank test. The correlation between pathologic complete response (pCR) status and event-free survival time will be assessed by Cox model with landmark approach.
Pathologic Complete Rate (pCR) Rate 24 months Defined as the percentage of patients in whom a pCR was confirmed by histopathologic review of the surgical specimen. Chi-square test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare pCR resection rate between two treatment arms. Sensitivity analysis will be conducted among patients in cohort 1) and cohort 2). The association between pCR rate and OS/progression free survival (PFS) will be assessed by log-rank test and Cox model.
Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE 1 year Overall adverse event rates will be compared between treatment groups using Chi-square test (or Fisher's exact test if the data in contingency table is sparse).
Trial Locations
- Locations (155)
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Levine Cancer Institute-SouthPark
🇺🇸Charlotte, North Carolina, United States
Levine Cancer Institute-Mallard Creek
🇺🇸Charlotte, North Carolina, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Atrium Health Lincoln/LCI-Lincoln
🇺🇸Charlotte, North Carolina, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Atrium Health Union/LCI-Union
🇺🇸Monroe, North Carolina, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Mission Hospital Inc-Memorial Campus
🇺🇸Asheville, North Carolina, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Atrium Health Stanly/LCI-Albemarle
🇺🇸Albemarle, North Carolina, United States
Levine Cancer Institute-Ballantyne
🇺🇸Charlotte, North Carolina, United States
New Hanover Regional Medical Center/Zimmer Cancer Center
🇺🇸Wilmington, North Carolina, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Edwards Comprehensive Cancer Center
🇺🇸Huntington, West Virginia, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
University of Cincinnati/Barrett Cancer Center
🇺🇸Cincinnati, Ohio, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸Antioch, California, United States
Kaiser Permanente-Redwood City
🇺🇸Redwood City, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Kaiser Permanente-Santa Rosa
🇺🇸Santa Rosa, California, United States
Kaiser Permanente-South Sacramento
🇺🇸Sacramento, California, United States
Kaiser Permanente - Sacramento
🇺🇸Sacramento, California, United States
Atrium Health University City/LCI-University
🇺🇸Charlotte, North Carolina, United States
Atrium Health Cabarrus/LCI-Concord
🇺🇸Concord, North Carolina, United States
NHRMC Radiation Oncology - 16th Street
🇺🇸Wilmington, North Carolina, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Kaiser Permanente-Fresno
🇺🇸Fresno, California, United States
Kaiser Permanente-Fremont
🇺🇸Fremont, California, United States
University Oncology Associates
🇺🇸Clovis, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Modesto
🇺🇸Modesto, California, United States
Southern Cancer Center PC-Mobile
🇺🇸Mobile, Alabama, United States
Kaiser Permanente-Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente-Richmond
🇺🇸Richmond, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente-San Francisco
🇺🇸San Francisco, California, United States
Kaiser Permanente San Leandro
🇺🇸San Leandro, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸San Jose, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Kaiser Permanente-San Rafael
🇺🇸San Rafael, California, United States
Southern Cancer Center PC-Springhill
🇺🇸Mobile, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Kaiser Permanente-South San Francisco
🇺🇸South San Francisco, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
Kaiser Permanente-Stockton
🇺🇸Stockton, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸Vacaville, California, United States
Kaiser Permanente-Vallejo
🇺🇸Vallejo, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸Walnut Creek, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Northwest Community Hospital
🇺🇸Arlington Heights, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
🇺🇸Highland Park, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸Naperville, Illinois, United States
Edward Hospital/Cancer Center?Plainfield
🇺🇸Plainfield, Illinois, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
🇺🇸Biddeford, Maine, United States
MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
🇺🇸Sanford, Maine, United States
Saint Agnes Hospital
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
McLaren Cancer Institute-Macomb
🇺🇸Mount Clemens, Michigan, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸Saint Cloud, Minnesota, United States
Ascension Saint Mary's Hospital
🇺🇸Saginaw, Michigan, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
NHRMC Radiation Oncology - Supply
🇺🇸Supply, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Pottstown Hospital
🇺🇸Pottstown, Pennsylvania, United States
Levine Cancer Institute-Rock Hill
🇺🇸Rock Hill, South Carolina, United States
Greenville Health System Cancer Institute-Faris
🇺🇸Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Eastside
🇺🇸Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Seneca
🇺🇸Seneca, South Carolina, 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
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
IMG Hematology Oncology 8505
🇺🇸Fairfax, Virginia, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
IMG Hematology Oncology 8501
🇺🇸Fairfax, Virginia, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
McLaren Cancer Institute-Northern Michigan
🇺🇸Petoskey, Michigan, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸Louisville, Kentucky, United States
Maine Medical Center- Scarborough Campus
🇺🇸Scarborough, Maine, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Atrium Health Cleveland/LCI-Cleveland
🇺🇸Shelby, North Carolina, United States