Pancreas CancerPhase 2CHECKPOINTNCT05435053
Irreversible Electroporation + Nivolumab for Patients With Metastatic Pancreatic Cancer
A Phase 2 study testing Nivolumab and Irreversible electroporation (IRE) in people with Pancreas Cancer, run by Ismail Gögenur at 1 site in Denmark.
Trial summary
The trial investigates the safety and efficacy of irreversible electroporation in combination with checkpoint inhibition in patients with metastatic pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Pancreas Cancer
- What is being tested?
- Nivolumab and Irreversible electroporation (IRE)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Sep 2022to 30 Aug 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated per protocol.
- 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.
- Women must not be breastfeeding
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.
- 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.
Who cannot join
- 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
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- 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
- History of cardiac arrhythmia
- Recent myocardial infarction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Irreversible Electroporation in Combination With Immune Checkpoint Inhibition, in Patients With Metastatic Pancreatic Cancer - A Prospective, Phase 2 Study
The trial investigates the safety and efficacy of irreversible electroporation in combination with checkpoint inhibition in patients with metastatic pancreatic cancer.
Read the 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.
- Conditions
- Pancreas Cancer
- Being tested
- Nivolumab, Irreversible electroporation (IRE)
- Keywords
- Irreversible electroporation, Immunotherapy, Nivolumab, Abscopal effect
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Every 2 weeks (3 mg/kg, maximum of 240 mg) for up to 24 weeks
Nivolumab is an immune checkpoint inhibitor (PD-1-inhibitor).
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Nivolumab; Device: Irreversible electroporation (IRE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months after start of treatment
Secondary outcomes (5)
Tumor response by CT
Based on CT chest/abdomen scans according to RECIST version 1.1
Measured: Baseline compared to 3 and 6 months after start of treatment
Tumor response by ultrasound
Based on contrast enhanced ultrasound (CEUS) utilizing the standardized and quantitative method Dynamic CEUS (DCEUS)
Measured: Baseline compared to 3 and 6 months after start of treatment
Progression free survival
In terms of months
Measured: From start of treatment until unequivocal disease progression, assessed up to 5 years
Overall survival
In terms of months
Measured: From start of treatment until unequivocal disease progression, assessed up to 5 years
Quality of life using EORTC QLQ-C30
EORTC QLQ-C30
Measured: Baseline compared to 14 days, 3 and 6 months after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2022
- Study start8 Sep 2022
- Primary completion30 Aug 2023
- Study completion30 Aug 2023
Why it stopped: The study was terminated on the basis on an evaluation of the safety and efficacy of the 9 included patients of which 2 of the patients were excluded before receiving any study treatments, thus 7 patients were treated in the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreas CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ismail Gögenur
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ismail Gögenur, Zealand University Hospital
- Investigators
- Ismail Gögenur, Professor, Principal investigator, Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05435053
- Sponsor's protocol ID
- 26092020
- Other IDs
- 2020-004623-17
- Acronym
- CHECKPOINT
- Status last verified
- Sep 2023
- First submitted
- 22 Jun 2022
- Last updated
- 15 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Irreversible Electroporation in Combination With Immune Checkpoint Inhibition, in Patients With Metastatic Pancreatic Cancer - A Prospective, Phase 2 Study
- ClinicalTrials.gov ID
- NCT05435053
- Acronym / sponsor ID
- CHECKPOINT / 26092020
- Conditions
- Pancreas Cancer
- Keywords
- Irreversible electroporation, Immunotherapy, Nivolumab, Abscopal effect
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated on the basis on an evaluation of the safety and efficacy of the 9 included patients of which 2 of the patients were excluded before receiving any study treatments, thus 7 patients were treated in the study.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Ismail GögenurUniversity, hospital or other
- Study start
- 8 Sep 2022 (actual)
- Primary completion
- 30 Aug 2023 (actual)
- Study completion
- 30 Aug 2023 (actual)
- First posted
- 28 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial investigates the safety and efficacy of irreversible electroporation in combination with checkpoint inhibition in patients with metastatic pancreatic cancer.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IRE + Nivolumab | Experimental | Drug: Nivolumab, Device: Irreversible electroporation (IRE)IRE on Day 1, followed by Nivolumab on Day 2/3 and then every 2 weeks (q2w) for a maximum of 24 weeks. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoEvery 2 weeks (3 mg/kg, maximum of 240 mg) for up to 24 weeks Nivolumab is an immune checkpoint inhibitor (PD-1-inhibitor). | Drug | IRE + Nivolumab |
| 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. | Device | IRE + Nivolumab |
Primary outcome
Incidence of treatment related adverse events [Safety and Tolerability]
Time frame: 6 months after start of treatment
Determined by the incidence and severity of treatment related adverse events according to CTCAE version 4.0
5 secondary outcomes
Tumor response by CT
Time frame: Baseline compared to 3 and 6 months after start of treatment
Tumor response by ultrasound
Time frame: Baseline compared to 3 and 6 months after start of treatment
Progression free survival
Time frame: From start of treatment until unequivocal disease progression, assessed up to 5 years
Overall survival
Time frame: From start of treatment until unequivocal disease progression, assessed up to 5 years
Quality of life using EORTC QLQ-C30
Time frame: Baseline compared to 14 days, 3 and 6 months after start of treatment
Results and safety
The study was stopped early (reason given: The study was terminated on the basis on an evaluation of the safety and efficacy of the 9 included patients of which 2 of the patients were excluded before receiving any study treatments, thus 7 patients were treated in the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ismail Gögenur, Professor principal investigator
Zealand University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Irreversible electroporation (IRE) in people with Pancreas Cancer, run by Ismail Gögenur at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated on the basis on an evaluation of the safety and efficacy of the 9 included patients of which 2 of the patients were excluded before receiving any study treatments, thus 7 patients were treated in the study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment related adverse events [Safety and Tolerability] (time frame: 6 months after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.