Irreversible Electroporation + Nivolumab for Patients With Metastatic Pancreatic Cancer

NCT05435053 | Terminated Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: 260920202020-004623-17
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pancreas Cancer

Keywords

Irreversible electroporation; Immunotherapy; Nivolumab; Abscopal effect

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment related adverse events [Safety and Tolerability]

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

  6 months after start of treatment

Secondary Outcomes (5)

• Tumor response by CT

  Baseline compared to 3 and 6 months after start of treatment

• Tumor response by ultrasound

  Baseline compared to 3 and 6 months after start of treatment

• Progression free survival

  From start of treatment until unequivocal disease progression, assessed up to 5 years

• Overall survival

  From start of treatment until unequivocal disease progression, assessed up to 5 years

• Quality of life using EORTC QLQ-C30

  Baseline compared to 14 days, 3 and 6 months after start of treatment

Study Arms (1)

IRE + Nivolumab

EXPERIMENTAL

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; Device: Irreversible electroporation (IRE)

Interventions

Nivolumab DRUG

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

Also known as: Opdivo

IRE + Nivolumab

Irreversible electroporation (IRE) DEVICE

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.

IRE + Nivolumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Histopathological confirmation of pancreatic adenocarcinoma.
• 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.
• Age \> 18 years
• Life expectancy greater than 3 months
• ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) 0-1
• 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

You may not qualify if:

• Malignant ascites that is clinically detectable by physical examination or is symptomatic.
• 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
• Radiotherapy, or major surgery within the last 2 weeks prior to entering the study
• 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.
• Patients should be excluded if they have an active, known or suspected autoimmune disease.
• 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
• 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.
• PD-1 inhibitors may cause hepatic toxicity which may lead to caution regarding other potentially hepatotoxic drugs.
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• 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
• Contraindications for IRE:
• Implanted pacemaker or ICD (Implantable cardioverter defibrillator) unit.
• History of epilepsy

Sponsors & Collaborators

• Ismail Gögenur: lead

Study Sites (1)

Zealand University Hospital

Roskilde, 4600, Denmark

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Electroporation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Study Officials

• Ismail Gögenur, Professor

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: June 28, 2022
• Study Start: September 8, 2022
• Primary Completion: August 30, 2023
• Study Completion: August 30, 2023
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)