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

NCT03970252

Description:

This phase I/II trial 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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Combination With Chemotherapy Before Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer
  • Official Title: A Pilot and Feasibility Study of PD-1 Blockade With Nivolumab in Combination With Chemotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 19-000290
  • SECONDARY ID: NCI-2019-02886
  • SECONDARY ID: 19-000290
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03970252

Conditions

  • Borderline Resectable Pancreatic Adenocarcinoma
  • Resectable Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
Fluorouracil5-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-2-9757Treatment (nivolumab, mFOLFIRINOX)
IrinotecanTreatment (nivolumab, mFOLFIRINOX)
Irinotecan HydrochlorideCampto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440ETreatment (nivolumab, mFOLFIRINOX)
LeucovorinFolinic acidTreatment (nivolumab, mFOLFIRINOX)
Leucovorin CalciumAdinepar, 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, WellcovorinTreatment (nivolumab, mFOLFIRINOX)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab, mFOLFIRINOX)
Oxaliplatin1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669Treatment (nivolumab, mFOLFIRINOX)

Purpose

This phase I/II trial 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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, mFOLFIRINOX)ExperimentalPatients 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.
  • Fluorouracil
  • Irinotecan
  • Irinotecan Hydrochloride
  • Leucovorin
  • Leucovorin Calcium
  • Nivolumab
  • Oxaliplatin

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Descriptive statistics with frequency and proportion will be used.

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

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