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

NCT04212026 | Terminated Phase 2 DMC

• 1 other identifier: PDAC-IRE
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Metastatic Pancreatic Cancer

Keywords

metastatic Pancreatic Cancer; Irreversible electroporation (IRE); nivolumab; Phase II trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Objective Response Rate (ORR) after the 5th dose of nivolumab of the primary tumor site (pancreas).

  At 2-4 weeks after the 5th dose of nivolumab

• ORR after the 5th dose of nivolumab of the IRE-treated liver metastasis

  At 2-4 weeks after the 5th dose of nivolumab

• ORR based on best overall response

  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

  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)

  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

Study Arms (1)

Nivolumab

EXPERIMENTAL

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. Two weeks after the last dose of nivolumab ("Week 8"), radiological restaging will be performed (="Week 10").

Drug: Nivolumab

Interventions

Nivolumab DRUG

The patients start treatment with nivolumab on day 1 after IRE and will be given nivolumab at a flat dose of 240 mg every 2 weeks (q2wk) for 5 cycles until Week 8.

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• measurable per RECIST v 1.1 (Appendix 1), AND
• at least two metastases ≥ 1 cm AND
• percutaneously accessible for repeat biopsy, AND
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• St. Clara Research Ltd.: collaborator

Study Sites (3)

Lindenhofspital

Bern, Canton of Bern, 3012, Switzerland

Location

St. Claraspital

Basel, 4058, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mathias Worni, MD

  Clarunis - St. Clara Hospital and University Hospital Basel

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot, multicenter, single-arm phase II trial.

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 26, 2019
• Study Start: June 28, 2020
• Primary Completion: July 12, 2023
• Study Completion: July 12, 2023
• Last Updated: July 18, 2023

Record last verified: 2023-07

Locations

CH (3)