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

NCT ID: NCT02459652

Last Updated: 2020-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-28

Study Completion Date

2018-07-17

Brief Summary

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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

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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.

Conditions

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Pancreatic Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

S-1

Intervention Type DRUG

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 Therapy

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Japan Agency for Medical Research and Development

OTHER_GOV

Sponsor Role collaborator

Pharma Valley Center

UNKNOWN

Sponsor Role collaborator

Japan Adjuvant Study Group of Pancreatic Cancer

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Masafumi Ikeda, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center Hospital East, Department of Hepatobiliary Pancreatic Oncology

Katsuhiko Uesaka, M.D., Ph.D.

Role: STUDY_CHAIR

Shizuoka Cancer Center Hospital

Locations

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Aichi Cancer Center

Nagoya, Aichi-ken, Japan

Site Status

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Site Status

Hirosaki University Hospital

Hirosaki, Aomori, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status

Fukuyama City Hospital

Fukuyama, Hiroshima, Japan

Site Status

National Hospital Organization Kure Medical Center

Kure, Hiroshima, Japan

Site Status

Asahikawa Medical University

Asahikawa, Hokkaido, Japan

Site Status

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status

Kobe University Hospital

Kobe, Hyōgo, Japan

Site Status

St. Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, Japan

Site Status

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status

National Hospital Organization Osaka National Hospital

Chuo-ku, Osaka, Japan

Site Status

Saitama Cancer Center

Kita-adachigun Inamachi, Saitama, Japan

Site Status

Seirei Mikatahara General Hospital

Hamamatsu, Shizuoka, Japan

Site Status

Shizuoka Cancer Center

Suntohgun, Nagaizumityo, Shizuoka, Japan

Site Status

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Site Status

Tochigi Cancer Center

Utsunomiya, Tochigi, Japan

Site Status

Tokyo Women's Medical University Hospital

Shinjuku, Tokyo, Japan

Site Status

Chiba Cancer Center

Chiba, , Japan

Site Status

National Hospital Organization Kyusyu Cancer Center

Fukuoka, , Japan

Site Status

Yamagata University Hospital

Yamagata, , Japan

Site Status

Countries

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Japan

References

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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.

Reference Type BACKGROUND
PMID: 29061632 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33065644 (View on PubMed)

Other Identifiers

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JASPAC 05

Identifier Type: -

Identifier Source: org_study_id