Neoadjuvant Chemoradiation in Patients With Borderline Resectable Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
Previous reports suggest benefit of neoadjuvant chemoradiation treatment for borderline resectable pancreas cancer. This study is a multicenter prospective randomized phase II/III study of neoadjuvant chemoradiation with gemcitabine in patients with borderline resectable pancreas cancer. The study is designed in 2 arms, one with upfront surgery and the other with neoadjuvant chemoradiation therapy.

Detailed Description
-----------------
Previous reports suggest benefit of neoadjuvant chemoradiation treatment for borderline resectable pancreas cancer. This study is a multicenter prospective randomized phase II/III study of neoadjuvant chemoradiation with gemcitabine in patients with borderline resectable pancreas cancer. The study is designed in 2 arms, one with upfront surgery and the other with neoadjuvant chemoradiation therapy. This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment.

Official Title
-----------------
Multicenter Prospective Randomized Phase II/III Study of Neoadjuvant Chemoradiation With Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Neoadjuvant chemoradiation
* Procedure: Upfront surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: >18 years old or <75 years old ECOG 0-2 biopsy proven adenocarcinoma of the pancreas no history of previous chemotherapy borderline resectable pancreas cancer no distant metastasis WBC at least 3,000/mm3 or absolute neutrophil count at least 1,500/mm3, Platelet count at least 125,000/mm3 Bilirubin less than 2.5 mg/dL AST less than 5 times upper limit of normal Creatinine no greater than 1.5 times upper limit of normal informed consent Exclusion Criteria: history of previous chemotherapy history of radiation at >25% area of bone marrow stage unspecified, with distant metastasis, recurrent pancreas cancer history of malignant neoplasm (except stage 0 cancer, skin in situ cancer except malignant melanoma). Patients who are NED after 5 years after treatment of malignant neoplasm can be candidate of this study pregnant, breast-feeding patient uncontrolled or active infection uncontrolled cardiopulmonary disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant<br>Neoadjuvant - operation - maintenance chemotherapy | Drug: Neoadjuvant chemoradiation<br>* Neoadjuvant chemoradiation; 45Gy/25fx + 9Gy/5fx of radiation over 6 weeks with Gemcitabine 400mg/㎡ 4 weeks rest, re-evaluation for resectability operation start maintenance chemotherapy within 4 6 weeks after operation with Gemcitabine 1000mg/㎡ (D1, 8, 15) every 4 weeks, for 4 cycle<br>|
| Active Comparator: Upfront surgery<br>Operation - adjuvant chemoradiation - maintenance chemotherapy | Procedure: Upfront surgery<br>* Operation at time of diagnosis Adjuvant chemoradiation; 45Gy/25fx + 9Gy/5fx of radiation over 6 weeks with Gemcitabine 400mg/㎡ start maintenance chemotherapy within 4 6 weeks after completion of adjuvant chemoradiation with Gemcitabine 1000mg/㎡ (D1, 8, 15) every 4 weeks, for 4 cycle<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year survival rate | 2-year actual survival outcome | 2-year actual survival outcome | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median survival | calculated from overall survival with Kaplan-Meier method | after at least of 2-years follow up of all participants | 
| 1-year survival rate | 1-year actual survival rate | after at least of 1-year follow up of all participants | 
| R0 resection rate | according to pathology report after operation | within 3 weeks after operation | 
| curative resection rate | according to pathology report after operation | within 3 weeks after operation | 
| local recurrence | any point during the follow-up period | within at least 2-years follow up | 
| response rate after neoadjuvant chemoradiation | comparison of imaging study findings at pre- and post-neoadjuvant chemoradiation | within 6 weeks after completion of neoadjuvant chemoradiation | 
| efficacy of imaging study after neoadjuvant chemoradiation | comparison of pathology report and imaging study in patients who completed neoadjuvant chemoradiation | within 3 weeks after operation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer, borderline resectable, locally advanced, resectability, chemotherapy, radiation, chemoradiation, neoadjuvant, survival, prognosis, recurrence, response rate, pancreas