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

Pancreatic Adenocarcinoma Clinical Trial

Official title:

Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02839343
• Other study ID #: A021501
• Secondary ID: NCI-2016-00456
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 2016

Study information

• Verified date: April 2022
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Borderline Resectable Adenocarcinoma of the Head of the Pancrease
• Pancreatic Adenocarcinoma

Intervention

Radiation:
• radiation therapy

Procedure:
• surgery

Drug:
• mFOLFIRINOX
oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV
• FOLFOX
oxaliplatin IV, leucovorin IV and 5-FU IV

Locations

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

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Rate	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.	18 months
Secondary	Residual Tumor (R)0 Resection Rate	Defined as the percentage of patients in whom an achieved R0 resection was achieved during surgery.	24 months
Secondary	Event-free Survival	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.	4 years and 7 months
Secondary	Pathologic Complete Rate (pCR) Rate	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.	24 months
Secondary	Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE	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).	1 year