A Single-arm Phase II Study to Evaluate the Safety and Efficacy of Combination Systematic Chemotherapy and Multiple Rounds of Endoscopic Ultrasound-guided Radiofrequency Ablation in Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The objectives of this study are to determine the feasibility, tolerability, and treatment effect of Endoscopic Ultrasound (EUS) Radiofrequency ablation (RFA) plus standard-of-care Neoadjuvant chemotherapy (NAC) in the treatment of Pancreatic Ductal Adenocarcinoma (PDAC). Endoscopic Ultrasound (EUS) Radiofrequency ablation (RFA) and Neoadjuvant chemotherapy (NAC) will be performed before tumor resection surgery, with the goal of shrinking a tumor or stopping the spread of cancer so that surgery might be less invasive and more effective.

Official Title
-----------------
A Single-arm Phase II Study to Evaluate the Safety and Efficacy of Combination Systematic Chemotherapy and Multiple Rounds of Endoscopic Ultrasound-guided Radiofrequency Ablation in Pancreatic Cancer

Conditions
-----------------
Pancreatic Ductal Adenocarcinoma (PDAC)

Intervention / Treatment
-----------------
* Device: Endoscopic Ultrasound (EUS)-Guided Radiofrequency Ablation (RFA)
* Drug: Neoadjuvant chemotherapy (NAC)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed and histologically confirmed PDAC by biopsy Permanent street address and consent to study participation Axial CT scan consistent with PDAC No prior chemotherapy or less than 2 months of pre-operative chemotherapy for PDAC. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Exclusion Criteria: No phone number of Male or Female patients > 18 years of age Diagnosed and histologically confirmed PDAC by biopsy No permanent street address or telephone number Pregnant patients Inmates or prisoners Unable to provide informed consent

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant chemotherapy (NAC) plus Endoscopic Ultrasound (EUS) Radiofrequency ablation (RFA)<br> | Device: Endoscopic Ultrasound (EUS)-Guided Radiofrequency Ablation (RFA)<br>* Endoscopic Ultrasound (EUS)-guided Radiofrequency Ablation (RFA) consists of the application of alternating current with a frequency of 350-500 kilohertz (kHz) to the target tissue via a special electrode located at the tip of an echoendoscope. The alternating current causes the vibratory movement of ionic particles in the abutting and adjoining tissue and results in the generation of heat. However, RFA induces not only local disruption of the tumor by heat, but it also produces localized coagulation necrosis of the tumor which induces the release of large amounts of cellular debris which represent a source of tumor antigens that can trigger a host adaptive immune response against the tumor.<br>Drug: Neoadjuvant chemotherapy (NAC)<br>* The NAC regimen will be determined clinically by the participant's physician [possible regimens are either mFOLFIRINOX or Gemcitabine Nab-Paclitaxel +/- Cisplatin (GemAbraxane)].<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who are able to complete neoadjuvant chemotherapy plus EUS-RFA and later undergo surgical tumor resection |  | From the time of EUS-RFA NAC intervention to the time of surgical tumor resection (about 5-6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic treatment response as assessed by standard Response evaluation criteria in solid tumors (RECIST) criteria | Using the RECIST criteria, treatment response is categorized as follows: Complete response (CR): Disappearance of all target lesions Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 2 months after the initiation of chemotherapy | 
| Radiographic treatment response as assessed by standard Response evaluation criteria in solid tumors (RECIST) criteria | Using the RECIST criteria, treatment response is categorized as follows: Complete response (CR): Disappearance of all target lesions Partial response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 4 months after the initiation of chemotherapy | 
| Number of participants with post-operative complications |  | from the time of surgical tumor resection to 90 days following surgical tumor resection | 
| Disease-free survival time | Disease is defined as clinical evidence of local or distant recurrence. | from the time of diagnosis to time of recurrence (or up to 5 years after diagnosis, whichever occurs first) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endoscopic Ultrasound Radiofrequency ablation (EUS-RFA)