2020-06-28
2023-07-12
2023-07-12
8
NCT04212026
University Hospital, Basel, Switzerland
University Hospital, Basel, Switzerland
INTERVENTIONAL
Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer.
This proof of concept trial aims to assess whether the combination of IRE with Nivolumab is safe and effective to treat metastatic pancreatic cancer, based on the available preliminary evidence that IRE is able to cause a systemic anti-tumor immune response (i.e. abscopal effect), which may enhance the effect of subsequent Nivolumab treatment. In addition, the trial aims to clarify the systemic effects of IRE over time and thereby to provide more insight in the mechanism of work of the technique.
The prognosis of patients newly diagnosed with pancreatic ductal adenocarcinoma (PDAC) is extremely poor with a 5-year overall survival rate of less than 5%. To improve this dismal outcome, new treatment approaches are urgently needed. So far, immune-checkpoint therapy was not successful in patients with PDAC. Given the poor response to conventional chemotherapy, there is an imperative need to make PDACs amenable to immune-checkpoint therapy. Irreversible electroporation (IRE) is a relatively novel and safe ablation technique that destroys tumors by using apoptosis-inducing electrical currents inducing local and systemic pro-inflammatory cytokine expression and enhances the presence of cytotoxic CD8+ T-cells, while the apoptotic cell material preserves neo-antigen properties detectable by dendritic cells. This effect might be further enhanced by immune-checkpoint therapy. The rationale of our study is to convert immunologically cold PDACs into hot PDACs by triggering an enhanced local and systemic immune response. We hypothesize that among patients with metastatic PDAC, the IRE of one liver metastasis followed by the administration of an immune-checkpoint inhibitor leads to a measurable radiological response in a selected non-treated liver metastasis. Furthermore, we hypothesize that the immune response is both local in the form of tumor infiltrating lymphocytes (TILS) and an immunologically activated tumor microenvironment in the IRE-treated metastasis, as well as systemic as evidenced by an abscopal response in the IRE-untreated metastatic and primary site. The objective of the trial is to examine whether for patients with metastatic PDAC the combination of IRE of one liver metastasis followed by the administration of five doses of nivolumab leads to a measurable radiological response in a selected non-treated liver metastasis. To demonstrate that the trial treatment leads to a measurable immune response, multiple translational research projects will assess the effect of IRE and nivolumab on the development of the local and peripheral tumor immune response over time.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates | Results Reporting Dates | Study Record Updates |
---|---|---|
2019-12-19 | N/A | 2023-07-14 |
2019-12-23 | N/A | 2023-07-18 |
2019-12-26 | N/A | 2023-07 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Na
Interventional Model:
Single Group
Masking:
None
Arms and Interventions
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Nivolumab Nivolumab treatment will be given every 2 weeks at a standard flat dose of 240 mg for a total of 5 doses, and the IRE procedure will be performed using the standard setting to ablate tumors at the level of the liver that is well tolerated by the patients. | DRUG: Nivolumab
|
Primary Outcome Measures | Measure Description | Time Frame |
---|---|---|
The objective response rate (ORR) after the 5th dose of nivolumab of the reference liver metastasis that was not biopsied. | The objective response rate (ORR) according to RECIST v1.1 after the 5th dose of nivolumab of the reference liver metastasis that was not biopsied, assessed 2-4 weeks after the 5th dose of nivolumab, defined as proportion of patients achieving Complete Response (CR) or Partial Response (PR). The assessment will be based on re-staging the patients with a CT-scan 2-4 weeks after the 5th dose of nivolumab. Patients without tumor assessment 2-4 weeks after the 5th dose of nivolumab will be counted as non-responders. | At 2-4 weeks after the 5th dose of nivolumab |
Secondary Outcome Measures | Measure Description | Time Frame |
---|---|---|
Objective Response Rate (ORR) after the 5th dose of nivolumab of the primary tumor site (pancreas). | The ORR according to RECIST v1.1 after the 5th dose of nivolumab of the primary tumor site (pancreas), assessed 2-4 weeks after the 5th dose of nivolumab, defined as percentage of patients achieving Complete Response (CR) or Partial Response (PR). Patients without tumor assessment 2-4 weeks after the 5th dose of nivolumab will be counted as non-responders. | At 2-4 weeks after the 5th dose of nivolumab |
ORR after the 5th dose of nivolumab of the IRE-treated liver metastasis | The ORR according to RECIST v1.1 after the 5th dose of nivolumab of IRE-treated liver metastasis, assessed 2-4 weeks after the 5th dose of nivolumab, defined as percentage of patients achieving CR or PR. Patients without tumor assessment 2-4 weeks after the 5th dose of nivolumab will be counted as non-responders. | At 2-4 weeks after the 5th dose of nivolumab |
ORR based on best overall response | The ORR based on best overall response according to RECIST v1.1, assessed at any time between registration and disease progression by RECIST v1.1, death, or subsequent anticancer therapy, whichever occurs first, defined as percentage of patients achieving CR or PR. | From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration |
Immune ORR (iORR) based on best overall immune response | The immune ORR (iORR) based on best overall immune response according to iRECIST, assessed at any time between registration and disease progression by iRECIST, death, or subsequent anticancer therapy, whichever occurs first, defined as percentage of patients achieving CR, PR, iCR or iPR. | From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration |
Progression free survival (PFS) | Progression-free survival (PFS), defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first. | From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration |
Immune PFS (iPFS) | Immune PFS (iPFS), defined as the time from registration until progression according to iRECIST (first iUPD without documented iSD, iPR or iCR thereafter) or death from any cause, whichever occurs first. Patients without event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment showing non-progression (before the start of the new therapy, if any). | From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration |
Overall survival (OS) | Overall survival (OS), defined as time form registration to death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known alive. | From the date of registration until the date of death, assessed up to 4 years after registration |
Adverse events | Adverse events, assessed according to NCI CTCAE v5.0 and Clavien-Dindo Classification for procedural complications | From the date of registration to 100 days after last trial treatment |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
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