PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer

Sponsor
Amsterdam UMC, location VUmc
Study ID
NCT04612530
Phase
PHASE1
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 100 Years
Healthy Volunteers
Not accepted

Interventions

  • Irreversible Electroporation (IRE) — DEVICE
    Irreversible electroporation (IRE) is a local ablative technique that utilizes electrical pulses to destroy tumor tissue
  • Nivolumab — DRUG
    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 — DRUG
    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.

Study Details

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.

Key Dates

Start date
Sep 1, 2020
Status verified
Dec 2022
Primary completion
Apr 1, 2023
Completion
Jun 1, 2023

Study Design

Enrollment
18 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A: Nivolumab
    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.
  • Experimental: Arm B: IRE + 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.
  • Experimental: Arm C: CpG + IRE + 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.

Primary Outcome Measure

Safety of the combination treatment IRE + immunotherapy based on adverse events [ Time Frame: From randomization until 1 year later ]

Central Contacts

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