Nivolumab In Combination With Chemotherapy Pre-Surgery In Treating Patients With Borderline Resectable Pancreatic Cancer

Study Overview

Nivolumab in Combination With Chemotherapy Pre-Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer

This pilot and feasibility study studies how well nivolumab and combination chemotherapy work before surgery in treating patients with pancreatic cancer that could possibly be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin, 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 nivolumab in combination with chemotherapy before surgery may work better in treating patients with pancreatic cancer compared to chemotherapy alone.

PRIMARY OBJECTIVES: I. To evaluate development of clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (FFX). II. To evaluate pathologic complete response after neoadjuvant nivolumab and FOLFIRINOX (FFX). SECONDARY OBJECTIVES: I. To evaluate early efficacy measured by percent change of CA 19-9 response rate, R0 resection rate, overall response rate (ORR) and disease free survival (DFS). EXPLORATORY OBJECTIVES, OTHER ASSESSMENTS: I. To determine degree of changes in the tumor microenvironment (TME) of nivolumab and modified (m) FFX on cell proliferation and apoptosis. OUTLINE: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2-3 months.

Borderline Resectable Pancreatic Adenocarcinoma
Resectable Pancreatic Ductal Adenocarcinoma

DRUG: Fluorouracil
DRUG: Irinotecan
DRUG: Irinotecan Hydrochloride
DRUG: Leucovorin
DRUG: Leucovorin Calcium
BIOLOGICAL: Nivolumab
DRUG: Oxaliplatin
PROCEDURE: Therapeutic Conventional Surgery

19-000290
NCI-2019-02886 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))

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 2019-05-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-08-08
First Submitted that Met QC Criteria 2019-05-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-08-09
First Posted (ACTUAL) 2019-05-31	Results First Posted N/A	Last Verified 2024-08

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 (nivolumab, mFOLFIRINOX) Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes o	DRUG: Fluorouracil Given IV DRUG: Irinotecan Given IV DRUG: Irinotecan Hydrochloride Given IV DRUG: Leucovorin Given IV DRUG: Leucovorin Calcium Given IV BIOLOGICAL: Nivolumab Given IV DRUG: Oxaliplatin Given IV PROCEDURE: Therapeutic Conventional Surgery Undergo surgery

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (nivolumab, mFOLFIRINOX)

Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes o

DRUG: Fluorouracil

Given IV

DRUG: Irinotecan

Given IV

DRUG: Irinotecan Hydrochloride

Given IV

DRUG: Leucovorin

Given IV

DRUG: Leucovorin Calcium

Given IV

BIOLOGICAL: Nivolumab

Given IV

DRUG: Oxaliplatin

Given IV

PROCEDURE: Therapeutic Conventional Surgery

Undergo surgery

Primary Outcome Measures	Measure Description	Time Frame
Clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (mFFX) chemotherapy	Descriptive statistics with frequency and proportion will be used.	Up to 3 years
Pathologic complete response after nivolumab and mFFX treatment	Descriptive statistics with frequency and proportion will be used.	Up to 3 years

Secondary Outcome Measures	Measure Description	Time Frame
Percent change of CA 19-9 response rate	Descriptive statistics with frequency and proportion will be used to analyze the CA19-9 response rate.	Baseline up to 3 years
R0 resection rate		Up to 3 years
Overall response rate (ORR)	Descriptive statistics with frequency and proportion will be used to analyze ORR.	Up to 3 years
Disease free survival (DFS)	Kaplan-Meier methods will be used to analyze DFS with median and 95% confidence interval (CI).	Up to 3 years
Incidence of adverse events	Will be categorized and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3.	Up to 28 days after last dose of study drug
Delayed wound healing		Up to 3 years
Wound dehiscence		Up to 3 years
Wound infection		Up to 3 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:

Histologically confirmed pancreatic adenocarcinoma
One of the following:

Borderline resectable disease. There are multiple definitions of borderline resectable pancreatic ductal adenocarcinoma (PDAC) including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on computed tomography (CT):

An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring >= 180 degrees of the circumference of the vessel wall
Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
An interface between the tumor and superior mesenteric artery (SMA) measuring < 180 degrees of the circumference of the vessel wall
Performance status of Eastern Cooperative Oncology Group (ECOG) of 0-1
Therapy naive
Absolute neutrophil count (ANC) >= 1500/mm^3
Platelets >= 100,000/mm^3
Hemoglobin >= 9 g/dl
Serum total bilirubin =< 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
Alkaline phosphatase =< 2.5 x ULN
Serum creatinine (sCr) =< 1.5 x ULN or creatinine clearance (Ccr) >= 40 mL/min as calculated by the modified Cockcroft-Gault formula
Peripheral neuropathy < grade 2

Locally advanced (clearly unresectable) or metastatic disease
Known status of human immunodeficiency virus (HIV) which is not well-controlled at the time of study eligibility
Untreated hepatitis B infection
Active infection or antibiotics within 48 hours prior to study
Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (patients with history of skin cancers excluding melanoma will be eligible for participation)
Serious medical comorbidities such as New York Heart Association class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a grade 2 or greater bleeding episode in the 3 weeks before day 1
Prior history of cerebrovascular accident or transient ischemic attack, or pre-existing carotid artery disease
Known pregnancy, nursing women or positive pregnancy test. Requirement for women of childbearing potential (WOCBP) must have a pregnancy test every 4 weeks and WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab
Any prisoners, or subjects who are compulsory detained are excluded
Any condition that would preclude informed consent, consistent follow-up and compliance for the study participation

Collaborators and Investigators

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

Bristol-Myers Squibb
NovoCure Ltd.

Investigators

PRINCIPAL_INVESTIGATOR: Zev A Wainberg, UCLA / Jonsson 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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