A Phase 1 interventional study of Irreversible Electroporation (IRE) and Nivolumab in Pancreatic Cancer and Metastatic Pancreatic Cancer, sponsored by Amsterdam UMC, location VUmc. Status unknown at 1 site in Netherlands. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2022-12-20.
Sponsored by Amsterdam UMC, location VUmc · Phase 1, Interventional, and Treatment
Irreversible electroporation is a local ablative technique used in the treatment of pancreatic cancer. In addition to its cytoreductive ability, IRE also induces a systemic immune response. However, this immune response is not potent enough to establish durable regression of the tumor. The immune response can be leveraged by combining IRE with immunotherapy. The primary aim of this study is to determine the safety of IRE + Nivolumab (arm B) and IRE + Nivolumab + CpG (arm C). The secondary aim is to assess efficacy of the experimental arms (B, C) and control arm A (Nivolumab monotherapy), based on overall and progression-free survival as well as locoregional and systemic immune modulation.
Pancreatic carcinoma is one of the deadliest types of cancer. In contrast to other cancers, new treatment options have demonstrated only moderate improvements for pancreatic cancer in terms of overall survival. Patients with metastasized disease (stage IV, AJCC) that are treated with chemotherapy in the Netherlands currently present a median overall survival of 6.4 months. Previous research has shown promising results for patients with locally advanced pancreatic cancer (LAPC, stage III, AJCC) with regards to combination treatment with chemotherapy and irreversible electroporation (IRE), a local ablation technique that utilizes electrical pulses to destroy cancerous tissue. In addition to an increase in overall survival, IRE induced a systemic immune response. However, the immune response was not potent enough to generate a lasting anti-tumor effect. Leveraging the body's own immune response by using local and systemic immunotherapy may create a synergistic effect, potentially inducing a durable anti-tumor response. The PANFIRE-III is a prospective randomised phase 1 trial with the primary aim to determine safety of the combination therapies IRE + Nivolumab (arm B) and CpG + IRE + Nivolumab (arm C) in patients with oligo-metastasized pancreatic cancer. The secondary goal is to determine efficacy of the experimental arms (arm B, C) compared to the control arm A (Nivolumab monotherapy). This will be assessed by looking at the overall and progression-free survival as well as the locoregional and systemic immune response. The treatment combination of IRE with immunotherapy has the potential to generate systemic protection by in vivo vaccination against pancreatic cancer cells, hereby inhibiting both local and distant tumor growth.
3,235 studies on the registry are indexed under Pancreatic Neoplasms; 899 are open to participants now.
This study's planned enrollment of 18 is below the median of 46 across 2,424 interventional studies indexed under Pancreatic Neoplasms.
Browse Pancreatic Neoplasms studies →Amsterdam UMC, location VUmc is the lead sponsor of 302 studies on the registry; 84 are open to participants now.
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Exclusion Criteria:
History of cardiac disease:
4 weeks after pre-treatment with FOLFIRINOX (4-8 cycles), the patient will start with the Nivolumab scheme. The first month, a biweekly dose of 240 mg will be administered, followed by a monthly dose of 480 mg. This treatment will continue until disease progression.
Drug: Nivolumab
4 weeks after pre-treatment with FOLFIRINOX (4-8 cycles), the patient will first receive (an incomplete) IRE of the primary pancreatic tumor. 2 weeks thereafter, they will start the Nivolumab scheme. The first month, a biweekly dose of 240 mg will be administered, followed by a monthly dose of 480 mg. This treatment will continue until disease progression.
Device: Irreversible Electroporation (IRE) · Drug: Nivolumab
4 weeks after pre-treatment with FOLFIRINOX (4-8 cycles), a toll-like receptor ligand (CpG) will be administered into the primary pancreatic tumor. A week later, the patient will receive (an incomplete) IRE of the primary tumor. 2 weeks thereafter, they will start the Nivolumab scheme. The first month, a biweekly dose of 240 mg will be administered, followed by a monthly dose of 480 mg. This treatment will continue until disease progression.
Device: Irreversible Electroporation (IRE) · Drug: Nivolumab · Drug: Toll-Like Receptor 9
Irreversible electroporation (IRE) is a local ablative technique that utilizes electrical pulses to destroy tumor tissue
Nivolumab is an immune checkpoint inhibitor targeting the PD-1 receptor on T-cells. Binding of the PD-1 monoclonal antibody onto the PD-1 receptor blocks the brake signal on the T-cells, allowing them to attack the cancer cells.
Toll-Like Receptor 9 (CpG) is an oligodeoxynucleotide that stimulates dendritic cells to release IFN type I, activating natural killer and infiltrating T cells. This creates a more pro-immunogenic tumor environment.
Safety of the combination treatment IRE + immunotherapy based on adverse events
Determined by the treatment related (serious) adverse events
Time frame: From randomization until 1 year later
Overall Survival
Overall survival in terms of months
Time frame: From date of randomization until death, assessed up to 5 years
Progression-Free Survival
Progression-free survival in terms of months
Time frame: From date of randomization until unequivocal disease progression, assessed up to 5 years
Immunomodulation (local)
The local immune response will be assessed using flow cytometry and immunohistochemistry of 2 biopsies (1x primary, 1x metastasis). Markers include those of T-cells, dendritic cells and others.
Time frame: Biopsies taken at T=0 (prior to treatment), T=2 weeks and T=6 weeks
Immunomodulation (systemic)
The systemic immune response will be assessed using flow cytometry of peripheral blood. Markers include those of T-cells, dendritic cells, MDSCs, NK cells.
Time frame: Blood taken at T=0 (prior to treatment), T=2 weeks and T=6 weeks
Tumor Response on Imaging
Tumor response will be assessed using PET-CT scans: tracer uptake of FDG and PD-L1. CT scans will be employed to determine tumor response based on the RECIST criteria.
Time frame: PET scans at T= 0 (prior to treatment), T= 6 weeks and T=3months. CT scans will be made at T= 0 (prior to treatment), T= 6 weeks, T=3months, followed by a scan every subsequent 3 months (T=6m,9m,12m etc) until unequivocal disease progression.
Quality of Life throughout treatment based on overall health
Based on the following EORTC questionnaire: EQ-5D-L5. Question types include: scale 1-5
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on specific health questions
Based on the following EORTC questionnaire: QLQ-C30 Question types include: scale 1-5, scale 1-7
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on Chemotherapy-Induced Peripheral Neuropathy
Based on the following EORTC questionnaire: QLQ-CIPN20 Question types include: scale 1-4
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment specifically in patients with pancreatic cancer
Based on the following EORTC questionnaire: QLQ-PAN26 Question types include: scale 1-4
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on the patient's happiness and emotional functioning
Based on the following questionnaire: QLQ-HAPINES Question types include: scale 1-10
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on anxiety and depression
Based on the following questionnaire: QLQ-HADS Question types include: scale 1-4
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on a patient's psychological state regarding their disease
Based on the following questionnaire: QLQ-WOPS Question types include: scale 1-4, scale 1-10, yes/no, open
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Quality of Life throughout treatment based on (decreased) pancreatic functionality
Based on the following questionnaire: EPI Question types include: 5 optional answers, scale, 1-4, scale 1-5, yes/no, open
Time frame: Quality of Life will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Pain based on the Visual Analog Score (VAS)
The pain questionnaire is based on the VAS and includes scale type questions (1 - 10) with higher scores referring to more pain.
Time frame: Pain will be assessed every 3 months (T=0 (baseline), T=3months, etc) up to 1 year
Plan to share: No
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Amsterdam UMC, location VUmc