- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03970252
Nivolumab in Combination With Chemotherapy Pre-Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer
A Pilot and Feasibility Study of PD-1 Blockade With Nivolumab in Combination With Chemotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
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 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.
|
Given IV
Other Names:
Undergo surgery
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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
Time Frame: Up to 3 years
|
Descriptive statistics with frequency and proportion will be used.
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Up to 3 years
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Pathologic complete response after nivolumab and mFFX treatment
Time Frame: Up to 3 years
|
Descriptive statistics with frequency and proportion will be used.
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Up to 3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent change of CA 19-9 response rate
Time Frame: Baseline up to 3 years
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Descriptive statistics with frequency and proportion will be used to analyze the CA19-9 response rate.
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Baseline up to 3 years
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R0 resection rate
Time Frame: Up to 3 years
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Up to 3 years
|
|
Overall response rate (ORR)
Time Frame: Up to 3 years
|
Descriptive statistics with frequency and proportion will be used to analyze ORR.
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Up to 3 years
|
Disease free survival (DFS)
Time Frame: Up to 3 years
|
Kaplan-Meier methods will be used to analyze DFS with median and 95% confidence interval (CI).
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Up to 3 years
|
Incidence of adverse events
Time Frame: Up to 28 days after last dose of study drug
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Will be categorized and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3.
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Up to 28 days after last dose of study drug
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Delayed wound healing
Time Frame: Up to 3 years
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Up to 3 years
|
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Wound dehiscence
Time Frame: Up to 3 years
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Up to 3 years
|
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Wound infection
Time Frame: Up to 3 years
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Up to 3 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in immune cell infiltrates and cancer cell IFNgamma signaling in response to FOLFIRINOX and nivolumab treatment
Time Frame: Baseline up to 3 years
|
Will examine the tissue from baseline to post-therapy at the time of surgery or at the time of progression.
Will use descriptive statistics and graphical displays to compare the percent change in stromal depletion overall and to describe the association with cell proliferation and death.
In addition, will graphically explore the percent change in stromal depletion for patients who undergo surgery compared to those who have disease progression.
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Baseline up to 3 years
|
Signaling and metabolomic changes in pancreatic ductal adenocarcinoma (PDAC) cancer cells that respond to IFNgamma
Time Frame: Baseline up to 3 years
|
Will examine the tissue from baseline to post-therapy at the time of surgery or at the time of progression.
Will use descriptive statistics and graphical displays to compare the percent change in stromal depletion overall and to describe the association with cell proliferation and death.
In addition, will graphically explore the percent change in stromal depletion for patients who undergo surgery compared to those who have disease progression.
|
Baseline up to 3 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Zev A Wainberg, UCLA / Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Micronutrients
- Vitamins
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Immune Checkpoint Inhibitors
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Hematinics
- Fluorouracil
- Oxaliplatin
- Nivolumab
- Leucovorin
- Irinotecan
- Calcium
- Levoleucovorin
- Folic Acid
- Calcium, Dietary
- Camptothecin
Other Study ID Numbers
- 19-000290
- NCI-2019-02886 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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