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

Pancreatic Cancer Clinical Trial

Official title:

Phase II Study of Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02459652
• Other study ID #: JASPAC 05
• Status: Completed
• Phase: Phase 2
• Start date: December 28, 2012
• Est. completion date: July 17, 2018

Study information

• Verified date: October 2020
• Source: Japan Adjuvant Study Group of Pancreatic Cancer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 17, 2018
• Est. primary completion date: May 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Japan	Asahikawa Medical University	Asahikawa	Hokkaido
Japan	Chiba Cancer Center	Chiba
Japan	National Hospital Organization Osaka National Hospital	Chuo-ku	Osaka
Japan	National Hospital Organization Kyusyu Cancer Center	Fukuoka
Japan	Fukuyama City Hospital	Fukuyama	Hiroshima
Japan	Seirei Mikatahara General Hospital	Hamamatsu	Shizuoka
Japan	Hirosaki University Hospital	Hirosaki	Aomori
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa
Japan	Saitama Cancer Center	Kita-adachigun Inamachi	Saitama
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	National Hospital Organization Kure Medical Center	Kure	Hiroshima
Japan	Shikoku Cancer Center	Matsuyama	Ehime
Japan	Aichi Cancer Center	Nagoya	Aichi
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Japan	Tokyo Women's Medical University Hospital	Shinjuku	Tokyo
Japan	Shizuoka Cancer Center	Suntohgun, Nagaizumityo	Shizuoka
Japan	Tochigi Cancer Center	Utsunomiya	Tochigi
Japan	Yamagata University Hospital	Yamagata
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa

Sponsors (3)

Lead Sponsor	Collaborator
Japan Adjuvant Study Group of Pancreatic Cancer	Japan Agency for Medical Research and Development, Pharma Valley Center

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View 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. 2020 Oct 15. doi: 10.1097/SLA.0000000000004535. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate	R0 resection rate of all patients enrolled in the study	Up to 4 years
Secondary	Overall survival		up to 6 years
Secondary	Disease-free survival		up to 6 years
Secondary	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
Secondary	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
Secondary	2-year survival rate		up to 6 years
Secondary	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
Secondary	Acute and late toxicity rates	All toxicities will be measured by CTCAE version 4.0.	With in 6 months
Secondary	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