Combination Chemotherapy Before And After Surgery In Treating Patients With Localized Pancreatic Cancer

Study Overview

Combination Chemotherapy Before and After Surgery in Treating Patients With Localized Pancreatic Cancer

This phase II trial studies how well combination chemotherapy before and after surgery works in treating patients with localized pancreatic cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PRIMARY OBJECTIVES: I. To determine the progression-free survival in patients with resectable non-metastatic pancreatic cancer treated with peri-operative modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX). SECONDARY OBJECTIVES: I. Determine overall survival. II. Determine objective response rate after neoadjuvant mFOLFIRINOX. TERTIARY OBJECTIVES: I. Compare R0 resection rate and pathologic stage with institutional historical controls who did not receive neoadjuvant therapy. II. Correlate early metabolic response, determined by changes in glucose metabolism using positron emission tomography (PET) scanning, with pathologic response, R0 resection, and pathologic stage. III. Correlate early metabolic response, determined by changes in glucose metabolism using PET scanning, with progression-free and overall survival. IV. Correlate pre-operative response of CA19-9 with progression-free and overall survival. V. Collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies. VI. Collect and bank tumor tissue from subjects prior to treatment (from the diagnostic endoscopic ultrasonography [EUS]-guided biopsy) and after treatment with six cycles of FOLFIRINOX (from the surgical specimen) for future correlative biomarker studies. OUTLINE: NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin intravenously (IV) over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection. ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Stage I Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer

DRUG: oxaliplatin
DRUG: leucovorin calcium
DRUG: irinotecan hydrochloride
DRUG: fluorouracil
PROCEDURE: therapeutic conventional surgery
OTHER: laboratory biomarker analysis

1306012255
NCI-2013-02349 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
1306012255 (OTHER Identifier) (OTHER: Yale University)
P30CA016359 (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 2014-01-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-11-09
First Submitted that Met QC Criteria 2014-01-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-11-13
First Posted (ACTUAL) 2014-01-28	Results First Posted N/A	Last Verified 2023-11

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 (mFOLFIRINOX) NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin IV over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every	DRUG: oxaliplatin Given IV DRUG: leucovorin calcium Given IV DRUG: irinotecan hydrochloride Given IV DRUG: fluorouracil Given IV PROCEDURE: therapeutic conventional surgery Undergo surgical resection OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (mFOLFIRINOX)

NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin IV over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every

DRUG: oxaliplatin

Given IV

DRUG: leucovorin calcium

Given IV

DRUG: irinotecan hydrochloride

Given IV

DRUG: fluorouracil

Given IV

PROCEDURE: therapeutic conventional surgery

Undergo surgical resection

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Progression free survival rate	Evaluated using a one-sided 0.10-alpha level exact test. Summarized using Kaplan-Meier curves	At 12 months

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival	Summarized using Kaplan-Meier curves.	Up to 5 years
Objective response rate		Up to 5 years

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:

Pathologic or cytologic documentation of pancreatic adenocarcinoma
Resectable pancreatic adenocarcinoma disease as defined as follows:

No evidence of extrapancreatic disease by cross sectional imaging, PET scan, or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases;
No evidence of tumor extension to superior mesenteric artery, hepatic artery, celiac axis, aorta, or inferior vena cava, and no evidence of occlusion or encasement of the superior mesenteric vein or superior mesenteric vein/portal vein confluence, as assessed by computed tomography (CT) using pancreatic protocol (or magnetic resonance imaging [MRI] in patients who cannot undergo CT) and EUS
No prior treatment (chemotherapy, biological therapy, or radiotherapy) for resectable pancreatic cancer
No prior treatment with oxaliplatin, irinotecan (irinotecan hydrochloride), fluorouracil or capecitabine
Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible
There is no evidence of the second malignancy at the time of study entry
> 4 weeks since major surgery
No other concurrent anticancer therapy
Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
No other malignancy within past five years except basal cell carcinoma of the skin, cervical carcinoma in situ, or non-metastatic prostate cancer
Paraffin block or slides must be available
Adequate organ function
No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
No >= grade 2 sensory peripheral neuropathy
No uncontrolled seizure disorder, active neurological disease, or known central nervous system (CNS) disease
No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
No history of chronic diarrhea
Not pregnant and not nursing
No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
Absolute neutrophil count >= 1,500/uL
Platelet count >= 100,000/uL
Hemoglobin >= 9 g/dL
Creatinine < 1.5 X upper limit of normal (ULN) or
Estimated glomerular filtration rate (GFR) > 30 ml/min
Bilirubin =< 1.5 X ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 X ULN
Negative pregnancy test in women of childbearing age

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Jill Lacy, MD, Yale University

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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Resources

Patients

Caregivers

Clinical Trial Record