Preoperative Folfirinox For Resectable Pancreatic Adenocarcinoma - A Phase II Study

Study Overview

Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

This phase II trial studies how well combination chemotherapy works in treating patients with pancreatic cancer before undergoing surgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, leucovorin calcium, and fluorouracil (FOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PRIMARY OBJECTIVES: I. To determine feasibility of preoperative FOLFIRINOX for resectable pancreatic adenocarcinoma. SECONDARY OBJECTIVES: I. To determine safety and toxicity of preoperative FOLFIRINOX. II. To determine response rate. III. To determine proportion achieving major pathologic response - per College of American Pathologists (CAP) criteria. IV. To determine proportion achieving R0 resection. V. To determine perioperative (30-day) mortality. VI. To determine the role of cancer antigen (CA)19.9 as potential prognostic and/or predictive biomarker. VII. To determine progression-free survival. VIII. To determine overall survival. OUTLINE: Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride intravenously (IV) over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Pancreatic Adenocarcinoma
Poorly Differentiated Malignant Neoplasm
Resectable Pancreatic Cancer
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Stage III Pancreatic Cancer
Undifferentiated Pancreatic Carcinoma

DRUG: Irinotecan Hydrochloride
DRUG: Oxaliplatin
DRUG: Leucovorin Calcium
DRUG: Fluorouracil
OTHER: Laboratory Biomarker Analysis

CASE4214
NCI-2014-02277 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CASE4214 (OTHER Identifier) (OTHER: Case Comprehensive Cancer Center)
P30CA043703 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-01-20	Results First Submitted 2018-06-13	Last Update Submitted that met QC Criteria 2018-06-13
First Submitted that Met QC Criteria 2015-01-20	Results First Submitted that Met QC Criteria 2018-06-13	Last Update Posted (ACTUAL) 2018-07-13
First Posted (ACTUAL) 2015-01-26	Results First Posted 2018-07-13	Last Verified 2018-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (FOLFIRINOX) Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatme	DRUG: Irinotecan Hydrochloride Given IV DRUG: Oxaliplatin Given IV DRUG: Leucovorin Calcium Given IV DRUG: Fluorouracil Given IV OTHER: Laboratory Biomarker Analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (FOLFIRINOX)

Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatme

DRUG: Irinotecan Hydrochloride

Given IV

DRUG: Oxaliplatin

Given IV

DRUG: Leucovorin Calcium

Given IV

DRUG: Fluorouracil

Given IV

OTHER: Laboratory Biomarker Analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Number of Patients Undergoing Surgical Resection After Receiving at Least 4 of the 6 Courses of Preoperative Chemotherapy	Proportion will be estimated using a binomial test.	Up to 12 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free Survival	Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves.	Up to 2 years
Overall Survival	Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves.	Up to 2 years
Incidence of Toxicities Greater Than Grade 2, Using the Common Terminology Criteria for Adverse Events Version 4.0	Toxicity evaluation will be enumeration of all major toxicities, with proportions calculated for each.	Up to 30 days after end of treatment or to the day prior to surgery
Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 2 years
Number of Participants Achieving Major Pathologic Response	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 2 years
Number of Participants Achieving R0 Resection	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 2 years
Number of Participants Experiencing Perioperative (30-day) Mortality	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 30 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have histologically or cytologically confirmed carcinoma of the pancreas; most cases will be adenocarcinoma; cases with "undifferentiated" or "poorly differentiated" carcinoma will also be eligible
There should be no evidence of metastatic disease on imaging of the chest, abdomen, and pelvis; this imaging should be either a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; positron emission tomography (PET) scans alone will not be adequate alternatives; there should be no evidence of occult metastatic disease in the abdomen, confirmed by laparoscopic examination
The primary tumor must be resectable, defined as no involvement (abutment or encasement) of the major arteries (celiac, common hepatic, superior mesenteric) and interface between tumor and vessel (portal, superior mesenteric veins) wall to be less than 180 degrees of the circumference of the vessel wall; this should be confirmed by imaging of the abdomen, either by a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; PET scans will not be adequate alternatives; for each patient, the resectability must be reviewed by one of the study surgeons
Patient must not have received any cancer-directed therapy (e.g., surgery, chemotherapy, radiation therapy, biologic therapy) for the index diagnosis
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Hemoglobin >= 10.0 g/dl
Absolute neutrophil count >= 1,500/mm^3
Platelet count >= 100,000/mm^3
Total bilirubin =< 1.5 X institutional upper limit of normal
Serum creatinine within normal institutional limits, or creatinine clearance (calculated by Cockcroft-Gault) >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Women of child-bearing potential and men must agree to use adequate contraception (double-barrier method of birth control or abstinence) for the duration of study participation and for 6 months after completing chemotherapy; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
Subjects must have the ability to understand and the willingness to sign a written informed consent document

Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or breastfeeding women
Pre-existing peripheral neuropathy (grade I or higher)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Davendra Sohal, Case Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record