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CHECKPOINT: Irreversible Electroporation + Nivolumab for Patients With Metastatic Pancreatic Cancer

Sponsor
Ismail Gögenur (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05435053
Collaborator
(none)
12
Enrollment
1
Arm
48
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The trial investigates the safety and efficacy of irreversible electroporation in combination with checkpoint inhibition in patients with metastatic pancreatic cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The trial is designed as an investigator initiated prospective phase 2 study in patients with metastatic pancreatic cancer (PC) to determine the efficacy and safety of checkpoint inhibition administered concurrently with irreversible electroporation.

A recently published preclinical study by Zhao et al. (2019) showed that the combination of IRE and PD-1-inhibitor suppressed the tumour growth and increased the survival of mice bearing pancreatic cancer.

The aim of the trial is to initiate an abscopal response, leveraging the patient's immune system in eliciting a sufficient immune response.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Irreversible Electroporation in Combination With Immune Checkpoint Inhibition, in Patients With Metastatic Pancreatic Cancer - A Prospective, Phase 2 Study
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Sep 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: IRE + Nivolumab

IRE on Day 1, followed by Nivolumab on Day 2/3 and then every 2 weeks (q2w) for a maximum of 24 weeks.

Drug: Nivolumab
Every 2 weeks (3 mg/kg, maximum of 240 mg) for up to 24 weeks Nivolumab is an immune checkpoint inhibitor (PD-1-inhibitor).
Other Names:
  • Opdivo

    • Device: Irreversible electroporation (IRE)
    Percutaneous ablation of a primary in-situ (or locally-recurrent) or metastatic lesion. Irreversible electroporation is delivered through the NanoKnife system (AngioDynamics, New York, USA). The system is FDA-approved for medical use.

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of treatment related adverse events [Safety and Tolerability] [6 months after start of treatment]

      Determined by the incidence and severity of treatment related adverse events according to CTCAE version 4.0

    Secondary Outcome Measures

    1. Tumor response by CT [Baseline compared to 3 and 6 months after start of treatment]

      Based on CT chest/abdomen scans according to RECIST version 1.1

    2. Tumor response by ultrasound [Baseline compared to 3 and 6 months after start of treatment]

      Based on contrast enhanced ultrasound (CEUS) utilizing the standardized and quantitative method Dynamic CEUS (DCEUS)

    3. Progression free survival [From start of treatment until unequivocal disease progression, assessed up to 5 years]

      In terms of months

    4. Overall survival [From start of treatment until unequivocal disease progression, assessed up to 5 years]

      In terms of months

    5. Quality of life using EORTC QLQ-C30 [Baseline compared to 14 days, 3 and 6 months after start of treatment]

      EORTC QLQ-C30

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Signed informed consent.

    2. Histopathological confirmation of pancreatic adenocarcinoma.

    3. At least one measurable primary in-situ (or locally-recurrent) or metastatic tumor must be present and, in the opinion of the investigators be amenable to IRE, and at least one additional metastatic tumor that will not undergo IRE. Both lesions must be accessible for image-guided percutaneous biopsy.

    4. Age > 18 years

    5. Life expectancy greater than 3 months

    6. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) 0-1

    7. Patients must have normal organ and marrow function as defined below:

    • White blood cell count (WBC) ≥ 2 x 10⁹/L

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L

    • Hemoglobin ≥ 5,6 mmol/l

    • Platelet count ≥ 100 x 10⁹/L

    • Serum bilirubin ≤1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L )

    • ASAT/ALAT ≤3 x ULN ( < 5 x ULN if known liver metastasis)

    • PP ≥ 40 or INR ≤ 1.5

    • Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 40 mL/min

    1. Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated per protocol.

    2. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.

    3. Women must not be breastfeeding

    4. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

    5. Men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

    Exclusion Criteria:

    1. Malignant ascites that is clinically detectable by physical examination or is symptomatic.

    2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways

    3. Radiotherapy, or major surgery within the last 2 weeks prior to entering the study

    4. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.

    5. Patients should be excluded if they have an active, known or suspected autoimmune disease.

    6. Patients should be excluded if they are positive test for hepatitis B virus surface anti-gen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

    7. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immuno-suppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

    8. PD-1 inhibitors may cause hepatic toxicity which may lead to caution regarding other potentially hepatotoxic drugs.

    9. Allergies and Adverse Drug Reaction

    • History of allergy to study drug components

    • History of severe hypersensitivity reaction to any monoclonal antibody

    1. Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

    2. Contraindications for IRE:

    • Implanted pacemaker or ICD (Implantable cardioverter defibrillator) unit.

    • History of epilepsy

    • History of cardiac arrhythmia

    • Recent myocardial infarction

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Ismail Gögenur

    Investigators

    • Principal Investigator: Ismail Gögenur, Professor, Zealand University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ismail Gögenur, Professor, Zealand University Hospital
    ClinicalTrials.gov Identifier:
    NCT05435053
    Other Study ID Numbers:
    • 26092020
    • 2020-004623-17
    First Posted:
    Jun 28, 2022
    Last Update Posted:
    Jun 28, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Ismail Gögenur, Professor, Zealand University Hospital
    Irreversible electroporation
    Immunotherapy
    Nivolumab
    Abscopal effect
    Additional relevant MeSH terms:
    Pancreatic Neoplasms
    Nivolumab

    Study Results

    No Results Posted as of Jun 28, 2022