Clinical trial NCT02839343: Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer
Official title: Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Borderline Resectable Adenocarcinoma of the Head of the Pancrease
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Sky Foundation
First posted: 2016-07-20
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival (OS) Rate
timeFrame: 18 months
Secondary outcomes:
measure: Residual Tumor (R)0 Resection Rate
timeFrame: 24 months
measure: Event-free Survival
timeFrame: 4 years and 7 months
measure: Pathologic Complete Rate (pCR) Rate
timeFrame: 24 months
measure: Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE
timeFrame: 1 year
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center PC-Mobile
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center PC-Springhill
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Antioch
country: United States
facility: Kaiser Permanente-Deer Valley Medical Center
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Clovis
country: United States
facility: University Oncology Associates
state: California
city: Fremont
country: United States
facility: Kaiser Permanente-Fremont
state: California
city: Fresno
country: United States
facility: Kaiser Permanente-Fresno
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Modesto
country: United States
facility: Kaiser Permanente-Modesto
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente-Redwood City
state: California
city: Richmond
country: United States
facility: Kaiser Permanente-Richmond
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente-South Sacramento
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente-San Francisco
state: California
city: San Jose
country: United States
facility: Kaiser Permanente-Santa Teresa-San Jose
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente San Leandro
state: California
city: San Rafael
country: United States
facility: Kaiser Permanente-San Rafael
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente-South San Francisco
state: California
city: Stockton
country: United States
facility: Kaiser Permanente-Stockton
state: California
city: Sunnyvale
country: United States
facility: Palo Alto Medical Foundation-Sunnyvale
state: California
city: Vacaville
country: United States
facility: Kaiser Permanente Medical Center-Vacaville
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem-Glenbrook Hospital
state: Illinois
city: Highland Park
country: United States
facility: NorthShore University HealthSystem-Highland Park Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital/Cancer Center
state: Illinois
city: Plainfield
country: United States
facility: Edward Hospital/Cancer Center?Plainfield
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Hospital-Westwood Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: The James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Biddeford
country: United States
facility: MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
state: Maine
city: Sanford
country: United States
facility: MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
state: Maine
city: Scarborough
country: United States
facility: Maine Medical Center- Scarborough Campus
state: Maine
city: Baltimore
country: United States
facility: Saint Agnes Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Cancer Institute-Macomb
state: Michigan
city: Petoskey
country: United States
facility: McLaren Cancer Institute-Northern Michigan
state: Michigan
city: Saginaw
country: United States
facility: Ascension Saint Mary's Hospital
state: Michigan
city: Saint Cloud
country: United States
facility: Coborn Cancer Center at Saint Cloud Hospital
state: Minnesota
city: Cape Girardeau
country: United States
facility: Southeast Cancer Center
state: Missouri
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Kearney
country: United States
facility: CHI Health Good Samaritan
state: Nebraska
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Albemarle
country: United States
facility: Atrium Health Stanly/LCI-Albemarle
state: North Carolina
city: Asheville
country: United States
facility: Mission Hospital Inc-Memorial Campus
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Lincoln/LCI-Lincoln
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute-SouthPark
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health University City/LCI-University
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute-Mallard Creek
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute-Ballantyne
state: North Carolina
city: Concord
country: United States
facility: Atrium Health Cabarrus/LCI-Concord
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Monroe
country: United States
facility: Atrium Health Union/LCI-Union
state: North Carolina
city: Shelby
country: United States
facility: Atrium Health Cleveland/LCI-Cleveland
state: North Carolina
city: Supply
country: United States
facility: NHRMC Radiation Oncology - Supply
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center/Zimmer Cancer Center
state: North Carolina
city: Wilmington
country: United States
facility: NHRMC Radiation Oncology - 16th Street
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati/Barrett Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital-Cedar Crest
state: Pennsylvania
city: Bethlehem
country: United States
facility: Saint Luke's University Hospital-Bethlehem Campus
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pottstown
country: United States
facility: Pottstown Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Faris
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Eastside
state: South Carolina
city: Rock Hill
country: United States
facility: Levine Cancer Institute-Rock Hill
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System Cancer Institute-Seneca
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: IMG Hematology Oncology 8501
state: Virginia
city: Fairfax
country: United States
facility: IMG Hematology Oncology 8505
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: The University of Texas MD Anderson Cancer Center
name: Matthew Katz, MD, FACS
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.