Neoadjuvant S-1 And Concurrent Radiotherapy For Borderline Resectable Pancreatic Cancer

Study Overview

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

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.

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

Pancreatic Cancer

DRUG: S-1
RADIATION: Radiation Therapy

JASPAC 05

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-05-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-10-25
First Submitted that Met QC Criteria 2015-05-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-10-27
First Posted (ACTUAL) 2015-06-02	Results First Posted N/A	Last Verified 2020-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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 medic	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.

Participant Group/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 medic

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.

Primary Outcome Measures	Measure Description	Time Frame
R0 resection rate	R0 resection rate of all patients enrolled in the study	Up to 4 years

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival		up to 6 years
Disease-free survival		up to 6 years
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.	Up to 4 years
Pathological response rate	Evaluation of the pathological response of the primary tumor was performed using a classification by Evans et al.	Up to 4 years
2-year survival rate		up to 6 years
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.	With in 90 days
Acute and late toxicity rates	All toxicities will be measured by CTCAE version 4.0.	With in 6 months
R0 resection rate in borderline resectable pancreatic cancer	Diagnosis of borderline resectable pancreatic cancer will be fixed by Diagnostic Radiology Central Review.	Up to 4 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
20 Years

Accepts Healthy Volunteers:

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,
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
Aspartate Transaminase (AST) and Alanine Transaminase (ALT)
serum albumin >/= 3.0 g/dl
serum creatinine
Creatinine clearance >/= 50 ml/min
Written informed consent

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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.

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