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

NCT ID: NCT03970252

Last Updated: 2024-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-24

Study Completion Date

2024-05-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Borderline Resectable Pancreatic Adenocarcinoma Resectable Pancreatic Ductal Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 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.

Group Type EXPERIMENTAL

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Leucovorin

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Fluorouracil

Given IV

Intervention Type DRUG

Irinotecan

Given IV

Intervention Type DRUG

Irinotecan Hydrochloride

Given IV

Intervention Type DRUG

Leucovorin

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Oxaliplatin

Given IV

Intervention Type DRUG

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 Irinomedac U-101440E Folinic acid Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec citrovorum factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

NovoCure Ltd.

INDUSTRY

Sponsor Role collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zev A Wainberg

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

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UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2019-02886

Identifier Type: REGISTRY

Identifier Source: secondary_id

19-000290

Identifier Type: -

Identifier Source: org_study_id

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