Clinical Trials /

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas.

NCT03767582

Description:

The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .

Related Conditions:
  • Pancreatic Adenocarcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas.
  • Official Title: A Phase I/II Trial of Combination Immunotherapy With Nivolumab and a CCR2/CCR5 Dual Antagonist (BMS-813160) With or Without GVAX Following Chemotherapy and Radiotherapy for Locally Advanced Pancreatic Ductal Adenocarcinomas (PDACs).

Clinical Trial IDs

  • ORG STUDY ID: J18163
  • SECONDARY ID: IRB00190660
  • NCT ID: NCT03767582

Conditions

  • Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)
  • Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
NivolumabOPDIVOPhase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
CCR2/CCR5 dual antagonistBMS-813160Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
GVAXPANC 10.05 pcDNA-1/GM-Neo vaccine, PANC 6.03 pcDNA-1/GM-Neo vaccinePhase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist

Purpose

The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .

Trial Arms

NameTypeDescriptionInterventions
Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonistExperimental
  • Nivolumab
  • CCR2/CCR5 dual antagonist
  • GVAX
Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonistExperimental
  • Nivolumab
  • CCR2/CCR5 dual antagonist
Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonistExperimental
  • Nivolumab
  • CCR2/CCR5 dual antagonist
  • GVAX

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years.

          -  Patients with histologically- or cytologically-proven, surgically unresectable,
             locally advanced pancreatic adenocarcinoma.

          -  If the patient does not have a diagnostic biopsy that is adequate for review at our
             institution, the patient must agree to a research core biopsy to be performed at Johns
             Hopkins.

          -  If the patient's available imaging is not adequate for review by our institution, the
             patient must agree to a repeat imaging to be performed at Johns Hopkins.

          -  Patients cannot have had any prior therapy for the locally advanced pancreatic
             adenocarcinoma.

          -  ECOG performance status 0 or 1

          -  Life expectancy greater than 3 months.

          -  Able to swallow pills or capsules.

          -  Patient must have adequate organ function defined by the study-specified laboratory
             tests.

          -  Patients must be eligible to receive FOLFIRINOX-based chemotherapy.

          -  Patients must be willing to be treated with stereotactic body radiation therapy (SBRT)
             only at Johns Hopkins Hospital.

          -  Patients must be willing to undergo a core biopsy of the pancreatic cancer.

          -  Patients must be willing to undergo a biopsy of the pancreatic cancer if the patient
             is not deemed a surgical candidate during the pre-surgical evaluation.

          -  Must use acceptable form of birth control while on study.

          -  Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Have had non-FOLFIRINOX-based chemotherapy for the pancreatic cancer.

          -  Have received any anti-neoplastic biologics, vaccines or hormonal treatment, including
             investigational drugs, within 28 days of the first dose of study.

          -  History of past treatment with immunotherapy agents prior to initial enrollment into
             this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1,
             anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 drugs).

          -  Have had prior organ or tissue allograft or allogeneic bone marrow transplantation,
             including corneal transplants.

          -  Is currently participating or has participated in a study of an investigational agent
             or using an investigational device for the treatment of cancer.

          -  Current use of immunosuppressive medications within 14 days prior to study
             medications.

          -  Have received any vaccine within 14 days prior to study medications.

          -  Receiving growth factors including, but not limited to, granulocyte-colony stimulating
             factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study
             medication.

          -  History of any autoimmune disease. Patients with thyroid disease will be allowed.

          -  Has a history of (non-infectious) pneumonitis or current pneumonitis.

          -  Has a pulse oximetry < 92% on room air.

          -  Requires the use of home oxygen.

          -  Patients with uncontrolled intercurrent illness including, but not limited to,
             myocardial infarction or stroke/transient ischemic attack within the past 6 months,
             uncontrolled infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  12-lead electrocardiogram with QRS ≥ 120 msec, except right bundle branch block ; QTcF
             (QT corrected for heart rate using Fridericia's method) ≥ 480 msec, except right
             bundle branch block

          -  Has an active infection requiring systemic therapy.

          -  Infection with HIV or hepatitis B or C.

          -  Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder
             cancer, early stage prostate cancer, or carcinoma in situ of the cervix.

          -  Current or recent (within 3 months of study treatment administration) gastrointestinal
             disease that could impact the absorption of study treatment.

          -  Any gastrointestinal surgery that is likely impact upon the absorption of study
             treatment.

          -  Inability to tolerate oral medication.

          -  Unable to have blood drawn.

          -  Have had surgery within 28 days of the first dose of study medication.

          -  Prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days of the first
             dose of BMS-813160.

          -  Prior use of Class I antiarrhythmics within 28 days of first dose of study medication.

          -  Has ascites requiring medical management.

          -  Presence of duodenal or gastric invasion by the tumor.

          -  Hypersensitivity reaction to any monoclonal antibody.

          -  Known allergy or hypersensitivity to study drugs or any of their components of the
             study arm that participant is enrolling.

          -  Woman who are pregnant or breastfeeding.

          -  Patient is unwilling or unable to follow the study schedule for any reason.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants experiencing study drug-related toxicities
Time Frame:3 years
Safety Issue:
Description:Number of participants who experienced study drug-related toxicities as defined by CTCAE v5.0

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:Number of months from the time of Cycle 1, Day 1 of immunotherapy until death from any cause
Measure:Metastasis free survival (MFS)
Time Frame:3 years
Safety Issue:
Description:Number of months from the time of Cycle 1, Day 1 of immunotherapy until first documented distant metastases on imaging per RECIST 1.1 or death from any cause, whichever occurs first.
Measure:Local progression free survival (LPFS) Time
Time Frame:3 years
Safety Issue:
Description:Number of months from the time of Cycle 1, Day 1 of immunotherapy until first documented local progression or relapse from complete response on imaging (using RECIST 1.1 criteria and irRECIST criteria) or death from any cause, whichever occurs first.
Measure:Surgical Resectability Rate
Time Frame:3 years
Safety Issue:
Description:Number of participants who are able to undergo successful tumor resection (as defined by R0 and R1 resection).
Measure:Pathological Response Rate
Time Frame:3 years
Safety Issue:
Description:Number of participants who have a pathologic complete response as determined by surgical margins and residual disease.
Measure:Change in Quality of life score based on EORTC QLQ-C30/Pan26
Time Frame:Baseline, 3 years
Safety Issue:
Description:Change in quality of life from baseline will be evaluated using the European Organization for Research and Treatment of Cancer core questionnaire, pancreatic cancer module (EORTC QLQ-C30/Pan26). The QLQ-C30 includes 30 questions assessing global health status/quality of life, function, and symptoms. The PAN26 module comprises of an additional 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). The score for each item ranges from 0-100, with a higher score reflecting a better level of functioning, a better quality of life, or a worse level of symptoms.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • GVAX
  • Nivolumab
  • CCR2/CCR5 dual antagonist
  • Anti-PD-1
  • Cancer vaccine
  • Monoclonal antibody
  • Checkpoint inhibitor
  • Myeloid modulating agent
  • Immunotherapy
  • Neoadjuvant chemotherapy
  • Stereotactic body radiation therapy
  • SBRT
  • Pancreatic cancer
  • Pancreatic Ductal Adenocarcinoma
  • PDAC
  • Locally advanced pancreatic ductal adenocarcinoma
  • LAPC

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