Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer.

• Register: ClinicalTrials.gov
• Last refreshed on: 25 July 2023
• Main ID: NCT04212026
• Date of registration: 19/12/2019
• Prospective Registration: Yes
• Primary sponsor: University Hospital, Basel, Switzerland
• Public title: Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer.
• Scientific title: Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer: a Multicenter Single-arm Phase II Trial
• Date of first enrolment: June 28, 2020
• Target sample size: 8
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04212026
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Switzerland

Contacts

• Name: Mathias Worni, MD
• Affiliation: Clarunis - St. Clara Hospital and University Hospital Basel

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent according to Swiss law and ICH GCP E6(R2) regulations before
registration and prior to any trial specific procedures.

- Pathologically proven PDAC with liver metastases either by histology or cytology.

- Liver metastases fulfilling the following criteria:

1. measurable per RECIST v 1.1 (Appendix 1), AND

2. at least two metastases = 1 cm AND

3. percutaneously accessible for repeat biopsy, AND

4. one of the biopsied metastases can be treated with IRE.

- At least stable disease after the completion of 10-24 weeks of first line standard
chemotherapy (either (m)FOLFIRINOX or Gemcitabine/Abraxane) as confirmed by tumor
assessment within 21 days prior to registration OR at least stable disease after the
completion of 10-24 weeks of second line standard chemotherapy (either (m)FOLFIRINOX
or Gemcitabine/Abraxane) as confirmed by tumor assessment within 21 days prior to
registration. The choice of chemotherapy regimen is based on the decision of the
treating medical oncologist.

- Patients with a prior malignancy and treated with curative intention are eligible if
all treatment of that malignancy was completed at least 2 years before registration
and the patient has no evidence of that disease at registration. Note: Less than 2
years is acceptable for malignancies with low risk of recurrence and/or no late
recurrence.

- Patients must be willing to participate in the translational research part of the
trial and to undergo a tumor biopsy of the primary tumor and of the two metastatic
sites in the liver before trial treatment and after five cycles of nivolumab
treatment.

- Patients must be willing to travel to the hospital where IRE and biopsy will be
performed (Claraspital Basel).

- Age = 18 years

- WHO performance status 0-1

- Life expectancy =4 months

- Adequate bone marrow function: neutrophil count = 1.0 x 109/L, platelet count = 100 x
109/L, hemoglobin = 80 g/L

- Adequate hepatic function: total bilirubin = 1.5 x ULN (except for patients with
Gilbert's disease = 3.0 x ULN), AST and ALT = 3 x ULN.

- Adequate renal function: estimated glomerular filtration rate (eGFR) = 50 mL/min/1.73
m2 (according to CKD-EPI formula).

- Adequate coagulation function: INR = 1.5 x ULN (the ULN for INR is defined with the
value 1.2 for all sites, in case no ULN is documented in the lab certificates/sheets).
In case patient is under anti-vitamin K treatment, INR >1.5 x ULN is allowed; however,
the patient has to be switched to LMWH treatment prior to any trial intervention.

- Women of childbearing potential must use effective contraception, are not pregnant or
lactating and agree not to become pregnant during trial treatment and until 5 months
after the last dose of nivolumab. A negative pregnancy test before inclusion into the
trial is required for all women of childbearing potential (for nivolumab product
information).

- Men agree not to donate sperm or to father a child during trial treatment and until 7
months after the last dose of nivolumab (for nivolumab product information).

Exclusion criteria:

- Clinically significant ascites that is not controllable.

- Prior radiotherapy to any PDAC disease site.

- Prior treatment with any immune checkpoint inhibitor.

- Concomitant or recent (within 100 days of registration) treatment with any other
experimental drug (enrollment in another clinical trial).

- Concomitant use of other anti-cancer drugs or radiotherapy.

- Severe or uncontrolled concurrent illness, such as cardiovascular disease (congestive
heart failure NYHA III or IV; unstable angina pectoris, history of myocardial
infarction within the last six months, serious arrhythmias requiring medication (with
exception of atrial fibrillation or paroxysmal supraventricular tachycardia),
significant QT-prolongation, uncontrolled hypertension.

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (i.v.) antimicrobial treatment.

- Known history of tuberculosis, known history of primary immunodeficiency, known
history of allogeneic organ transplant, receipt of live attenuated vaccine within 30
days prior to registration.

- Concomitant or prior use of immunosuppressive medication within 30 days of
registration, with the exceptions of intranasal and inhaled corticosteroids, or
systemic corticosteroids which must not exceed 10 mg/day of prednisone (or a dose
equivalent corticosteroid), and the premedication for chemotherapy

- Concomitant need for full anticoagulation treatment that cannot be stopped or bridged
for the performance of the biopsy/IRE procedures Note: Aspirin or other
acetylsalicylic acid containing drugs (up to 300 mg/day) are allowed

- Any concomitant drugs contraindicated for use with the trial treatment according to
the approved product information

- Known hypersensitivity to nivolumab or to any component of nivolumab, to stainless
steel or to contrast agents.

- Any other serious underlying medical (in particular coagulation deficiencies),
psychiatric, psychological, familial or geographical condition, which in the judgment
of the investigator may interfere with the planned staging, treatment and follow-up,
affect patient compliance or place the patient at high risk from treatment-related
complications.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Pancreatic Cancer

Intervention(s)

Drug: Nivolumab

Primary Outcome(s)

The objective response rate (ORR) after the 5th dose of nivolumab of the reference liver metastasis that was not biopsied. [Time Frame: At 2-4 weeks after the 5th dose of nivolumab]

Secondary Outcome(s)

ORR based on best overall response [Time Frame: 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]

Adverse events [Time Frame: From the date of registration to 100 days after last trial treatment]

Immune PFS (iPFS) [Time Frame: 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]

ORR after the 5th dose of nivolumab of the IRE-treated liver metastasis [Time Frame: At 2-4 weeks after the 5th dose of nivolumab]

Objective Response Rate (ORR) after the 5th dose of nivolumab of the primary tumor site (pancreas). [Time Frame: At 2-4 weeks after the 5th dose of nivolumab]

Progression free survival (PFS) [Time Frame: 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 [Time Frame: 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) [Time Frame: From the date of registration until the date of death, assessed up to 4 years after registration]

Secondary ID(s)

PDAC-IRE

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

St. Clara Research Ltd.