Neoadjuvant Chemoradiation in Patients With Borderline Resectable Pancreatic Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Neoadjuvant chemoradiation; Procedure: Upfront surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Gyeonggi
    • Goyang, Gyeonggi, Korea, Republic of, 410-769
      • Center for Liver Cancer, National Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant; Neoadjuvant - operation - maintenance chemotherapy	Drug: Neoadjuvant chemoradiation; 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
Active Comparator: Upfront surgery; Operation - adjuvant chemoradiation - maintenance chemotherapy	Procedure: Upfront surgery; 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

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Jin-Young Jang, M.D., Ph.D., Seoul National University College of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimate): October 25, 2011

Study Record Updates

• Last Update Posted (Actual): May 2, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: neoadjuvant; chemotherapy; cancer; pancreas; prognosis; survival; radiation; response rate; recurrence; chemoradiation; borderline resectable; locally advanced; resectability
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: BorderlinePancreas