Irreversible electroporation (NanoKnife) in combination with immunotherapy for non-curable pancreatic cancer
- Conditions
- Patients with non-curable pancreatic cancerMedDRA version: 20.0Level: LLTClassification code 10033575Term: Pancreas cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004623-17-DK
- Lead Sponsor
- Zealand University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
Inclusion criteria
•Signed informed consent.
•Able to understand spoken and written Danish
•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.
•Must have been exposed to first line chemotherapy before entering the protocol
•Age > 18 years
•Life expectancy greater than 3 months
•ECOG/WHO Performance Status (PS) 0-1
•Patients must have normal organ and marrow function as defined below:
-White blood cell count (WBC) = 2 x 10?/L
-Absolute neutrophil count (ANC) = 1.5 x 10?/L
-Hemoglobin = 5,6 mmol/l
-Platelet count = 100 x 10?/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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
Exclusion Criteria
•Malignant ascites that is clinically detectable by physical examination or is sympto-matic.
•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 Tcell 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 administra-tion, 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
•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 topi-cal 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 metas-tases. 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 unit.
History of epilepsy
History of cardiac arrhythmia
Recent myocardial infarction
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the safety of irreversibel electroporation in combination with nivolumab;Secondary Objective: To evaluate immune infiltration in tumor and the systemic immune respons;Primary end point(s): •To evaluate the safety of immune checkpoint inhibition (PD-1 inhibition, nivolumab), in combination with IRE.;Timepoint(s) of evaluation of this end point: Patient are admittet for observation 24 hours after IRE. <br>Patients are evaluated before 2nd. dose af nivolumab
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •To evaluate the efficacy of immune checkpoint inhibition, in combination with IRE as an additive treatment to standard of care.<br>•To evaluate tumor response through functional MRI <br>•To evaluate tumor response through contrast enhanced ultrasound (CEUS) utilizing the standardized and quantitative method Dynamic CEUS (DCEUS) <br><br>•To evaluate the mechanism of action in combination therapy of immune checkpoint inhibition with IRE.<br>•Progression free survival <br>•Overall survival<br>•Determining pain scores using numeric rating scale (NRS), at baseline and during fol-low-up.<br>•Investigating quality of life by questionnaire (EORTC QLQ-c30)<br>;Timepoint(s) of evaluation of this end point: Scans and quality of life questionnaires are collected every 8 weeks untill 8 weeks after last dose. <br>Immunologic response will be evaluated at the end of study