Pancreatic Locally Advanced Irresectable Cancer Ablation

Study Overview
=================
Brief Summary
-----------------
The aim of the PELICAN trial is to investigate the survival benefit of RFA plus standard palliative chemotherapy as compared to palliative chemotherapy alone in patients with LAPC after 2 months of induction chemotherapy.

Detailed Description
-----------------
Pancreatic cancer is the fifth leading cause of cancer-related death in the Netherlands. Each year around 900 patients in the Netherlands are diagnosed with irresectable locally advanced pancreatic cancer (LAPC), which has a median survival of 7.9 months. Standard treatment is palliative chemotherapy, which offers only a very limited survival benefit. Radiofrequency ablation (RFA) is a new ablative technique for LAPC, which is feasible and safe and has been suggested to improve survival. A randomized controlled trial has not yet been performed. The aim of the PELICAN trial is to investigate the survival benefit of RFA plus standard palliative chemotherapy as compared to palliative chemotherapy alone in patients with LAPC after 2 months of induction chemotherapy. In a randomized controlled parallel-group superiority multicenter phase III clinical trial. The intervention will be RFA followed by chemotherapy (gemcitabine monotherapy, nab-paclitaxel plus gemcitabine or FOLFIRINOX). The comparison will be standard palliative treatment consisting of gemcitabine monotherapy, nab-gemcitabine plus gemcitabine or FOLFIRINOX Primary endpoint: Overall survival. Secondary endpoints: Progression free survival, complications, pain, radiological tumor response, CA-19.9 and CEA response, quality of life, immunomodulation and total direct and indirect costs.

Official Title
-----------------
Pancreatic Locally Advanced Irresectable Cancer Ablation; a Randomized Controlled Superiority Phase III Multicenter Trial

Conditions
-----------------
Locally Advanced Pancreatic Cancer

Intervention / Treatment
-----------------
* Procedure: Radiofrequency ablation (RFA)
* Drug: FOLFIRINOX
* Drug: Nab-paclitaxel plus Gemcitabine
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the pancreas Locally irresectable tumor Primary tumor Stable disease or partial response after 2 months of induction chemotherapy (according to RECIST) Fit for chemotherapy as assessed by the medical oncologist, plus: Absolute neutrophil count: 1.5 × 109/L Platelet count: 100 × 109/L Renal function: creatinine clearance> 50 ml/min Transaminases ≤ 3 x ULN Fit for surgery assessed by the treating surgeon and anesthesiologist RFA technical feasible Written informed consent Age ≥ 18 years Expert panel approval for randomisation Exclusion Criteria: WHO performance status ≥ 3 Distant metastases on abdominal or thoracic CT scan* Previous surgical, local ablative or radiotherapy for pancreatic cancer or chemotherapy which is inconsistent with the prescribed induction schedule according to protocol** Stenosis of > 50% of the hepatic artery AND stenosis of >50% of the portal vein/ superior mesenteric vein Second primary malignancy, except adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix uteri or other malignancies treated at least 5 years previously without signs of recurrence. Pregnancy Positive regional lymph nodes metastases are not a reason for exclusion. Lymph nodes are considered as regional, according to the consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Suspicious lymph nodes only on radiologic basis are not considered as metastasis. Only when suspicion is high due to large infiltration, pathological examination by FNA can be considered. Surgical exploration is not a contra-indication for inclusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Radiofrequency ablation (RFA) plus chemotherapy versus chemotherapy monotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RFA<br>RFA: laparotomy is performed followed by radiofrequency ablation of the tumor. After recovery of the RFA patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel + gemcitabine or gemcitabine monotherapy | Procedure: Radiofrequency ablation (RFA)<br>* RFA involves the implantation of electrodes directly into the tumor, with the use of intra-operative ultrasound. The electrodes produce a high frequency alternating current, which leads to frictional heating and thus tissue destruction by thermal coagulation and protein denaturation.<br>* Other names: Celon ProSurge bipolar probe;Drug: FOLFIRINOX<br>* Oxaliplatin 85mg/m2 given as 2-hour IV infusion, followed by leucovorin 400mg/m2 given as 2-hour IV infusion with addition of irinotecan 180mg/m2 given as 90-minute IV infusion. Followed by fluorouracil 400mg/m2 IV bolus, followed by continuous IV infusion of 2400mg/m2 during 46-hour. Every 2 weeks.<br>Drug: Nab-paclitaxel plus Gemcitabine<br>* Nab-paclitaxel 125mg/m2 given as 30-40-minute IV infusion, followed by gemcitabine 1000mg/m2 IV infusion. On day 1, 8 and 15 every 4 weeks.<br>Drug: Gemcitabine<br>* Gemcitabine 1000mg/m2 given as 30-minute IV infusion. On day 1, 8 and 15 every 4 weeks.<br>|
| Active Comparator: Chemotherapy<br>Patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel plus gemcitabine or gemcitabine monotherapy | Drug: FOLFIRINOX<br>* Oxaliplatin 85mg/m2 given as 2-hour IV infusion, followed by leucovorin 400mg/m2 given as 2-hour IV infusion with addition of irinotecan 180mg/m2 given as 90-minute IV infusion. Followed by fluorouracil 400mg/m2 IV bolus, followed by continuous IV infusion of 2400mg/m2 during 46-hour. Every 2 weeks.<br>Drug: Nab-paclitaxel plus Gemcitabine<br>* Nab-paclitaxel 125mg/m2 given as 30-40-minute IV infusion, followed by gemcitabine 1000mg/m2 IV infusion. On day 1, 8 and 15 every 4 weeks.<br>Drug: Gemcitabine<br>* Gemcitabine 1000mg/m2 given as 30-minute IV infusion. On day 1, 8 and 15 every 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The period of time between randomization and death from any cause | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | The period of time between randomization and disease progression or death (by any cause) | 1.5 years | 
| Complications | The occurence of any post-operative complications | 1.5 years | 
| Radiological tumor response | The radiologic tumor response between start of study treatment till end of follow up (or death) | 1.5 years | 
| Tumor marker response | The response of the tumor marker between start of study treatment till end of follow up (or death) | 1.5 years | 
| Quality of Life questionnaire | The quality of life measured between start study treatment till end of follow up (or death) | 1.5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pancreatic cancer, Pancreatic neoplasms, Locally advanced pancreatic cancer, Radiofrequency ablation, Chemotherapy