Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03970252
Other study ID # 19-000290
Secondary ID NCI-2019-02886
Status Active, not recruiting
Phase Early Phase 1
First received
Last updated
Start date July 24, 2019
Est. completion date April 2026

Study information

Verified date May 2024
Source Jonsson Comprehensive Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 28
Est. completion date April 2026
Est. primary completion date April 15, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms

  • Adenocarcinoma
  • Borderline Resectable Pancreatic Adenocarcinoma
  • Resectable Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
Fluorouracil
Given IV
Irinotecan
Given IV
Irinotecan Hydrochloride
Given IV
Leucovorin
Given IV
Leucovorin Calcium
Given IV
Biological:
Nivolumab
Given IV
Drug:
Oxaliplatin
Given IV
Procedure:
Therapeutic Conventional Surgery
Undergo surgery

Locations

Country Name City State
United States UCLA / Jonsson Comprehensive Cancer Center Los Angeles California

Sponsors (3)

Lead Sponsor Collaborator
Jonsson Comprehensive Cancer Center Bristol-Myers Squibb, NovoCure Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Changes in immune cell infiltrates and cancer cell IFNgamma signaling in response to FOLFIRINOX and nivolumab treatment 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
Other Signaling and metabolomic changes in pancreatic ductal adenocarcinoma (PDAC) cancer cells that respond to IFNgamma 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
Primary 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
Primary Pathologic complete response after nivolumab and mFFX treatment Descriptive statistics with frequency and proportion will be used. Up to 3 years
Secondary 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
Secondary R0 resection rate Up to 3 years
Secondary Overall response rate (ORR) Descriptive statistics with frequency and proportion will be used to analyze ORR. Up to 3 years
Secondary Disease free survival (DFS) Kaplan-Meier methods will be used to analyze DFS with median and 95% confidence interval (CI). Up to 3 years
Secondary 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
Secondary Delayed wound healing Up to 3 years
Secondary Wound dehiscence Up to 3 years
Secondary Wound infection Up to 3 years
See also
  Status Clinical Trial Phase
Recruiting NCT04940286 - Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer Phase 2
Active, not recruiting NCT02446093 - Neoadjuvant CAN-2409 in Combination With Chemoradiation or SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2
Completed NCT02394535 - Nab-Paclitaxel, Capecitabine, and Radiation Therapy Following Induction Chemotherapy in Treating Patients With Locally Advanced Pancreatic Cancer Phase 1
Suspended NCT05688215 - Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma Phase 1/Phase 2
Recruiting NCT05083247 - Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2
Active, not recruiting NCT04484909 - NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer Phase 1
Terminated NCT05546411 - A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer Phase 2
Active, not recruiting NCT04423731 - Neoadjuvant Chemotherapy in Borderline Resectable and Locally Advanced Pancreatic Cancer
Active, not recruiting NCT04669197 - Study of Paclitaxel Protein Bound + Gemcitabine + Cisplatin + Hydrochloroquine as Treatment in Untreated Pancreas Cancer Phase 2
Recruiting NCT04106856 - Losartan and Hypofractionated Rx After Chemo for Tx of Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (SHAPER) Phase 1
Recruiting NCT05825066 - Neoadjuvant Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma Phase 2
Not yet recruiting NCT04915417 - Neoadjuvant Stereotactic Ablative Radiotherapy for Pancreatic Ductal Adenocarcinoma N/A
Recruiting NCT05356039 - Survival, Quality of Life and Resectability in Locally Advanced Pancreatic Cancer
Active, not recruiting NCT04481204 - New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study Phase 2