Clinical trial NCT02343835: Anti-Tumor Immunity Induced by IRE of Unresectable Pancreatic Cancer
Official title: IRE: Anti-Tumor Immunity Induced by IRE of Unresectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatic Cancer
Lead sponsor: Fuda Cancer Hospital, Guangzhou
Sponsor class: OTHER
First posted: 2015-01-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This protocol will study the impact of Irreversible electroporation (IRE) on immune response in patients diagnosed with unresectable pancreatic cancers smaller than 5.0 cm. It will profile the immune response to IRE of unresectable pancreatic cancers. The intra-tumoral and systemic immune response to IRE will be determined and compared to pre-ablated pancreatic cancer specimens and historical control specimens.

Detailed description: Thirty patients with histologically confirmed locally advanced pancreatic adenocarcinoma (≤5.0cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. Blood will be drawn for research before IRE. Blood and tissue samples will be used.

After IRE, patients will be carefully monitored and systemic immune responses are registered. Follow-up will consist of frequent CT and MRI scanning, as well as serum CA19.9 tumor marker and quality of life questionnaires and overall survival (OS).

The investigators hypothesize that IRE in the pancreas will induce good symptom palliation without causing severe complications as well as perfect systemic immune response.

Eligibility criteria: Inclusion Criteria:

* Radiologic confirmation of unresectable pancreatic cancer by at least CT of chest and abdomen
* Screening must be performed no longer than 2 weeks prior to study inclusion
* Maximum tumor diameter ≤ 5 cm;
* Histological or cytological confirmation of pancreatic adenocarcinoma;
* Age ≥ 18 years;
* ASA-classification 0 - 3
* Life expectancy of at least 12 weeks;
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion;

  * Hemoglobin ≥ 5.6 mmol/L;
  * Absolute neutrophil count (ANC) ≥ 1,500/mm3;
  * Platelet count ≥ 100\*109/l;
  * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
  * ALT and AST ≤ 2.5 x ULN;
  * Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 50 ml/min;
  * Prothrombin time or INR \< 1.5 x ULN;
  * Activated partial thromboplastin time \< 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician);
* Written informed consent;

Exclusion Criteria:

* Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
* Successful down staging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
* History of epilepsy;
* History of cardiac disease:

  * Congestive heart failure \>NYHA class 2;
  * Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
  * Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted);
* Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
* Compromised liver function (e.g. signs of portal hypertension, INR \> 1,5 without use of anticoagulants, ascites);
* Uncontrolled infections (\> grade 2 NCI-CTC version 3.0);
* Pregnant. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
* Immunotherapy ≤ 6 weeks prior to the procedure;
* Chemotherapy ≤ 6 weeks prior to the procedure;
* Radiotherapy ≤ 6 weeks prior to the procedure;
* Concomitant use of anti-convulsive and anti-arrhythmic drugs (other than beta blockers used for antihypertensive);
* Allergy to contrast media;
* Any implanted stimulation device;
* Any implanted metal stent/device within the area of ablation that cannot be removed;
* Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study; Of note, patients with contra-indications for MRI will not be excluded from participation: in this case radiologic follow-up will consist of CT-scanning according to protocol.

Primary outcomes:
measure: Characterization of the intra-tumoral and systemic immune response to IRE in unresectable pancreatic cancers
timeFrame: 12 Months
Secondary outcomes:
measure: Comparison immune response between non-ablated and ablated pancreatic cancer and pre-ablated and post ablated serum
timeFrame: 24 Months
Other outcomes:
measure: Overall survival and (local and distant) progression-free survival.
timeFrame: 60 Months
Locations:
city: Guangzhou
country: China
facility: FUDA Cancer Hospital
state: Guangdong
Study officials:
affiliation: FUDA Cancer Hospital
name: Lizhi l Niu, M.D.,PHD.
role: STUDY_CHAIR
References: