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Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
S-1
Radiation Therapy
Sponsored by
Japan Adjuvant Study Group of Pancreatic Cancer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Borderline Resectable Pancreatic Cancer

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Cytologic or histologic proof of pancreatic ductal carcinoma or adenosquamous carcinoma is required prior to study entry.
  • Disease assessment by Multi Detector-row Computed Tomography (MDCT) scan within 2 weeks of study entry
  • Borderline resectable pancreatic cancer
  • No evidence of metastatic disease as determined by chest CT scan, and abdominal CT scan and laparoscopy. Paraaortic lymph node metastasis is considered as metastatic.
  • Age >/=20 years old, </=75 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • No prior chemotherapy or radiotherapy for pancreatic cancer
  • A square 10 x 10 cm radiation field could encompass all pancreatic lesions and lymph node metastases
  • Adequate oral intake
  • Appropriate biliary drainage for obstructive jaundice

  • Lab Values:

    • hemoglobin concentration >/= 9.0 g/dL
    • leukocyte count >/= 3,000/mm3
    • platelet count >/= 100,000/mm3
    • serum total bilirubin </= 2.0 mg dL, or </=3.0 mg/dL with biliary drainage
    • Aspartate Transaminase (AST) and Alanine Transaminase (ALT) </= 100 U/L, or </= 150 U/L with biliary drainage
    • serum albumin >/= 3.0 g/dl
    • serum creatinine </= 1.2 mg dL
    • Creatinine clearance >/= 50 ml/min
  • Written informed consent

Exclusion Criteria:

  • Tumor invasion to the alimentary tract determined by abdominal CT scan or endoscopic examination
  • Prior chemotherapy using fluoropyrimidine
  • Prior radiation therapy to the abdomen
  • Watery diarrhea
  • Concurrent phenytoin, warfarin potassium, or flucytosine treatment
  • Presence of contrast medium allergy
  • Pulmonary fibrosis or interstitial pneumonia
  • Pleural effusion or ascites
  • Active infection
  • Uncontrolled diabetes mellitus (FBS >/= 200mg/dL or HbA1c >/= 10.0)
  • Active concomitant malignancy
  • Active gastroduodenal ulcer
  • Severe complications such as cardiac or renal disease
  • Regular administration of systemic corticosteroid
  • Psychiatric disorder
  • History of drug hypersensitivity
  • Pregnant and lactating women and women of childbearing age who were not using effective contraception

Sites / Locations

  • Aichi Cancer Center
  • Nagoya University Hospital
  • Hirosaki University Hospital
  • National Cancer Center Hospital East
  • Shikoku Cancer Center
  • Fukuyama City Hospital
  • National Hospital Organization Kure Medical Center
  • Asahikawa Medical University
  • Hokkaido University Hospital
  • Kobe University Hospital
  • St. Marianna University School of Medicine Hospital
  • Kanagawa Cancer Center
  • National Hospital Organization Osaka National Hospital
  • Saitama Cancer Center
  • Seirei Mikatahara General Hospital
  • Shizuoka Cancer Center
  • Jichi Medical University Hospital
  • Tochigi Cancer Center
  • Tokyo Women's Medical University Hospital
  • Chiba Cancer Center
  • National Hospital Organization Kyusyu Cancer Center
  • Yamagata University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant S-1/RT

Arm Description

This is a single arm prospective study. All eligible subjects will receive neoadjuvant S-1 and concurrent radiation followed by surgical resection. Subjects may receive adjuvant chemotherapy after surgical resection at the clinical discretion of the medical oncologists.

Outcomes

Primary Outcome Measures

R0 resection rate
R0 resection rate of all patients enrolled in the study

Secondary Outcome Measures

Overall survival
Disease-free survival
Response rate after neoadjuvant chemoradiation
All responses will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 within 4 weeks after completion of neoadjuvant therapy.
Pathological response rate
Evaluation of the pathological response of the primary tumor was performed using a classification by Evans et al.
2-year survival rate
Surgical morbidity rates
Both Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and Clavien-Dindo Classification will be used for all morbidity assessments.
Acute and late toxicity rates
All toxicities will be measured by CTCAE version 4.0.
R0 resection rate in borderline resectable pancreatic cancer
Diagnosis of borderline resectable pancreatic cancer will be fixed by Diagnostic Radiology Central Review.

Full Information

First Posted
May 29, 2015
Last Updated
October 25, 2020
Sponsor
Japan Adjuvant Study Group of Pancreatic Cancer
Collaborators
Japan Agency for Medical Research and Development, Pharma Valley Center
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1. Study Identification

Unique Protocol Identification Number
NCT02459652
Brief Title
Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer
Official Title
Phase II Study of Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 28, 2012 (Actual)
Primary Completion Date
May 13, 2016 (Actual)
Study Completion Date
July 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Japan Adjuvant Study Group of Pancreatic Cancer
Collaborators
Japan Agency for Medical Research and Development, Pharma Valley Center

4. Oversight

5. Study Description

Brief Summary
Multicenter Prospective Phase II Study for Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer RATIONALE: Borderline resectable pancreatic cancer is frequently related to a positive surgical margin and has a poor prognosis after resection. Neoadjuvant chemoradiation with intensive local effect may lead to substantial local control and prolongation of survival in borderline resectable pancreatic cancer. PURPOSE: This phase II trial assess efficacy and safety of neoadjuvant S-1 and concurrent radiotherapy for borderline resectable pancreatic cancer.
Detailed Description
S-1: S-1 is an oral fluorinated pyrimidine agent which contains tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydropyrimidine (CHDP) and potassium oxonate (Oxo) effective for gastric and various other types of cancers. S-1 is also active for pancreatic cancer: S-1 demonstrated non-inferiority to gemcitabine in overall survival for metastatic or locally advanced pancreatic cancer (LAPC). S-1 and Concurrent radiotherapy: S-1 therapy with concurrent radiation therapy (RT) had favorable activity with overall tumor response rate of 37%, as well as mild toxicity in patients with LAPC. The median survival time and the 2-year survival rate for LAPC patients treated by S-1/RT were 16.2 months and 26% respectively. Definition of Borderline Resectable Pancreatic Cancer:(1) Reconstructible bilateral impingement of superior mesenteric vein or portal vein; (2) Tumor contact with the superior mesenteric artery (SMA) of </= 180 degrees ; (3) Tumor contact with the common hepatic artery of </= 180 degrees (at the root of the gastroduodenal artery); and (4) Tumor contact with the celiac axis of </= 180 degrees. Tumor with portal vein tumor thrombus and tumor contact with the second or further jejunal SMA branch are considered as unresectable. Tumor which is contact with the common hepatic artery or celiac axis but can be resected by distal pancreatectomy with en bloc celiac axis resection, is not included in this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Borderline Resectable Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant S-1/RT
Arm Type
Experimental
Arm Description
This is a single arm prospective study. All eligible subjects will receive neoadjuvant S-1 and concurrent radiation followed by surgical resection. Subjects may receive adjuvant chemotherapy after surgical resection at the clinical discretion of the medical oncologists.
Intervention Type
Drug
Intervention Name(s)
S-1
Intervention Description
S-1 is administered orally at a dose of 40 mg/m2 twice daily on the day of irradiation (Monday through Friday) during radiation therapy.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
Radiation therapy is delivered with >6-megavolts (MV) photons, using a multiple field technique. A total dose of 50.4 Gy is delivered in 28 fractions over 5.5 weeks.
Primary Outcome Measure Information:
Title
R0 resection rate
Description
R0 resection rate of all patients enrolled in the study
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
up to 6 years
Title
Disease-free survival
Time Frame
up to 6 years
Title
Response rate after neoadjuvant chemoradiation
Description
All responses will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 within 4 weeks after completion of neoadjuvant therapy.
Time Frame
Up to 4 years
Title
Pathological response rate
Description
Evaluation of the pathological response of the primary tumor was performed using a classification by Evans et al.
Time Frame
Up to 4 years
Title
2-year survival rate
Time Frame
up to 6 years
Title
Surgical morbidity rates
Description
Both Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and Clavien-Dindo Classification will be used for all morbidity assessments.
Time Frame
With in 90 days
Title
Acute and late toxicity rates
Description
All toxicities will be measured by CTCAE version 4.0.
Time Frame
With in 6 months
Title
R0 resection rate in borderline resectable pancreatic cancer
Description
Diagnosis of borderline resectable pancreatic cancer will be fixed by Diagnostic Radiology Central Review.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytologic or histologic proof of pancreatic ductal carcinoma or adenosquamous carcinoma is required prior to study entry. Disease assessment by Multi Detector-row Computed Tomography (MDCT) scan within 2 weeks of study entry Borderline resectable pancreatic cancer No evidence of metastatic disease as determined by chest CT scan, and abdominal CT scan and laparoscopy. Paraaortic lymph node metastasis is considered as metastatic. Age >/=20 years old, </=75 years old Eastern Cooperative Oncology Group (ECOG) performance status 0-1 No prior chemotherapy or radiotherapy for pancreatic cancer A square 10 x 10 cm radiation field could encompass all pancreatic lesions and lymph node metastases Adequate oral intake Appropriate biliary drainage for obstructive jaundice Lab Values: hemoglobin concentration >/= 9.0 g/dL leukocyte count >/= 3,000/mm3 platelet count >/= 100,000/mm3 serum total bilirubin </= 2.0 mg dL, or </=3.0 mg/dL with biliary drainage Aspartate Transaminase (AST) and Alanine Transaminase (ALT) </= 100 U/L, or </= 150 U/L with biliary drainage serum albumin >/= 3.0 g/dl serum creatinine </= 1.2 mg dL Creatinine clearance >/= 50 ml/min Written informed consent Exclusion Criteria: Tumor invasion to the alimentary tract determined by abdominal CT scan or endoscopic examination Prior chemotherapy using fluoropyrimidine Prior radiation therapy to the abdomen Watery diarrhea Concurrent phenytoin, warfarin potassium, or flucytosine treatment Presence of contrast medium allergy Pulmonary fibrosis or interstitial pneumonia Pleural effusion or ascites Active infection Uncontrolled diabetes mellitus (FBS >/= 200mg/dL or HbA1c >/= 10.0) Active concomitant malignancy Active gastroduodenal ulcer Severe complications such as cardiac or renal disease Regular administration of systemic corticosteroid Psychiatric disorder History of drug hypersensitivity Pregnant and lactating women and women of childbearing age who were not using effective contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Masafumi Ikeda, M.D., Ph.D.
Organizational Affiliation
National Cancer Center Hospital East, Department of Hepatobiliary Pancreatic Oncology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Katsuhiko Uesaka, M.D., Ph.D.
Organizational Affiliation
Shizuoka Cancer Center Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Aichi Cancer Center
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Nagoya University Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Hirosaki University Hospital
City
Hirosaki
State/Province
Aomori
ZIP/Postal Code
036-8563
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Shikoku Cancer Center
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Fukuyama City Hospital
City
Fukuyama
State/Province
Hiroshima
ZIP/Postal Code
721-8511
Country
Japan
Facility Name
National Hospital Organization Kure Medical Center
City
Kure
State/Province
Hiroshima
ZIP/Postal Code
737-0023
Country
Japan
Facility Name
Asahikawa Medical University
City
Asahikawa
State/Province
Hokkaido
ZIP/Postal Code
078-8510
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
St. Marianna University School of Medicine Hospital
City
Kawasaki
State/Province
Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
National Hospital Organization Osaka National Hospital
City
Chuo-ku
State/Province
Osaka
ZIP/Postal Code
540-0006
Country
Japan
Facility Name
Saitama Cancer Center
City
Kita-adachigun Inamachi
State/Province
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
Seirei Mikatahara General Hospital
City
Hamamatsu
State/Province
Shizuoka
ZIP/Postal Code
433-8558
Country
Japan
Facility Name
Shizuoka Cancer Center
City
Suntohgun, Nagaizumityo
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Jichi Medical University Hospital
City
Shimotsuke
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Tochigi Cancer Center
City
Utsunomiya
State/Province
Tochigi
ZIP/Postal Code
320-0834
Country
Japan
Facility Name
Tokyo Women's Medical University Hospital
City
Shinjuku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Chiba Cancer Center
City
Chiba
ZIP/Postal Code
260-8717
Country
Japan
Facility Name
National Hospital Organization Kyusyu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Yamagata University Hospital
City
Yamagata
ZIP/Postal Code
990-9585
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
29061632
Citation
Takahashi S, Ohno I, Ikeda M, Kobayashi T, Akimoto T, Kojima M, Konishi M, Uesaka K. Neoadjuvant S-1 with concurrent radiotherapy followed by surgery for borderline resectable pancreatic cancer: study protocol for an open-label, multicentre, prospective phase II trial (JASPAC05). BMJ Open. 2017 Oct 22;7(10):e018445. doi: 10.1136/bmjopen-2017-018445.
Results Reference
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PubMed Identifier
33065644
Citation
Takahashi S, Ohno I, Ikeda M, Konishi M, Kobayashi T, Akimoto T, Kojima M, Morinaga S, Toyama H, Shimizu Y, Miyamoto A, Tomikawa M, Takakura N, Takayama W, Hirano S, Otsubo T, Nagino M, Kimura W, Sugimachi K, Uesaka K. Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05). Ann Surg. 2022 Nov 1;276(5):e510-e517. doi: 10.1097/SLA.0000000000004535. Epub 2020 Oct 15.
Results Reference
background

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Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer

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