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

Sponsor
Japan Adjuvant Study Group of Pancreatic Cancer (Other)
Overall Status
Completed
CT.gov ID
NCT02459652
Collaborator
Japan Agency for Medical Research and Development (Other), Pharma Valley Center (Other)
57
Enrollment
22
Locations
1
Arm
66.6
Actual Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
57 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer
Actual Study Start Date :
Dec 28, 2012
Actual Primary Completion Date :
May 13, 2016
Actual Study Completion Date :
Jul 17, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Neoadjuvant S-1/RT

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.

Drug: S-1
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.

Radiation: Radiation Therapy
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.

Outcome Measures

Primary Outcome Measures

  1. R0 resection rate [Up to 4 years]

    R0 resection rate of all patients enrolled in the study

Secondary Outcome Measures

  1. Overall survival [up to 6 years]

  2. Disease-free survival [up to 6 years]

  3. Response rate after neoadjuvant chemoradiation [Up to 4 years]

    All responses will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 within 4 weeks after completion of neoadjuvant therapy.

  4. Pathological response rate [Up to 4 years]

    Evaluation of the pathological response of the primary tumor was performed using a classification by Evans et al.

  5. 2-year survival rate [up to 6 years]

  6. Surgical morbidity rates [With in 90 days]

    Both Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and Clavien-Dindo Classification will be used for all morbidity assessments.

  7. Acute and late toxicity rates [With in 6 months]

    All toxicities will be measured by CTCAE version 4.0.

  8. R0 resection rate in borderline resectable pancreatic cancer [Up to 4 years]

    Diagnosis of borderline resectable pancreatic cancer will be fixed by Diagnostic Radiology Central Review.

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Aichi Cancer Center Nagoya Aichi Japan 464-8681
2 Nagoya University Hospital Nagoya Aichi Japan 466-8560
3 Hirosaki University Hospital Hirosaki Aomori Japan 036-8563
4 National Cancer Center Hospital East Kashiwa Chiba Japan 277-8577
5 Shikoku Cancer Center Matsuyama Ehime Japan 791-0280
6 Fukuyama City Hospital Fukuyama Hiroshima Japan 721-8511
7 National Hospital Organization Kure Medical Center Kure Hiroshima Japan 737-0023
8 Asahikawa Medical University Asahikawa Hokkaido Japan 078-8510
9 Hokkaido University Hospital Sapporo Hokkaido Japan 060-8648
10 Kobe University Hospital Kobe Hyogo Japan 650-0017
11 St. Marianna University School of Medicine Hospital Kawasaki Kanagawa Japan 216-8511
12 Kanagawa Cancer Center Yokohama Kanagawa Japan 241-8515
13 National Hospital Organization Osaka National Hospital Chuo-ku Osaka Japan 540-0006
14 Saitama Cancer Center Kita-adachigun Inamachi Saitama Japan 362-0806
15 Seirei Mikatahara General Hospital Hamamatsu Shizuoka Japan 433-8558
16 Shizuoka Cancer Center Suntohgun, Nagaizumityo Shizuoka Japan 411-8777
17 Jichi Medical University Hospital Shimotsuke Tochigi Japan 329-0498
18 Tochigi Cancer Center Utsunomiya Tochigi Japan 320-0834
19 Tokyo Women's Medical University Hospital Shinjuku Tokyo Japan 162-8666
20 Chiba Cancer Center Chiba Japan 260-8717
21 National Hospital Organization Kyusyu Cancer Center Fukuoka Japan 811-1395
22 Yamagata University Hospital Yamagata Japan 990-9585

Sponsors and Collaborators

  • Japan Adjuvant Study Group of Pancreatic Cancer
  • Japan Agency for Medical Research and Development
  • Pharma Valley Center

Investigators

  • Principal Investigator: Masafumi Ikeda, M.D., Ph.D., National Cancer Center Hospital East, Department of Hepatobiliary Pancreatic Oncology
  • Study Chair: Katsuhiko Uesaka, M.D., Ph.D., Shizuoka Cancer Center Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Japan Adjuvant Study Group of Pancreatic Cancer
ClinicalTrials.gov Identifier:
NCT02459652
Other Study ID Numbers:
  • JASPAC 05
First Posted:
Jun 2, 2015
Last Update Posted:
Oct 27, 2020
Last Verified:
Oct 1, 2020
Keywords provided by Japan Adjuvant Study Group of Pancreatic Cancer
Borderline Resectable Pancreatic Cancer
Additional relevant MeSH terms:
Pancreatic Neoplasms

Study Results

No Results Posted as of Oct 27, 2020