Clinical trial NCT02459652: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Borderline Resectable Pancreatic Cancer
Lead sponsor: Japan Adjuvant Study Group of Pancreatic Cancer
Sponsor class: OTHER
Collaborators: name: Japan Agency for Medical Research and Development
name: Pharma Valley Center
First posted: 2015-06-02
Enrollment: 57
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: R0 resection rate
timeFrame: Up to 4 years
Secondary outcomes:
measure: Overall survival
timeFrame: up to 6 years
measure: Disease-free survival
timeFrame: up to 6 years
measure: Response rate after neoadjuvant chemoradiation
timeFrame: Up to 4 years
measure: Pathological response rate
timeFrame: Up to 4 years
measure: 2-year survival rate
timeFrame: up to 6 years
measure: Surgical morbidity rates
timeFrame: With in 90 days
measure: Acute and late toxicity rates
timeFrame: With in 6 months
measure: R0 resection rate in borderline resectable pancreatic cancer
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
state: Ehime
city: Fukuyama
country: Japan
facility: Fukuyama City Hospital
state: Hiroshima
city: Kure
country: Japan
facility: National Hospital Organization Kure Medical Center
state: Hiroshima
city: Asahikawa
country: Japan
facility: Asahikawa Medical University
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Chuo-ku
country: Japan
facility: National Hospital Organization Osaka National Hospital
state: Osaka
city: Kita-adachigun Inamachi
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Hamamatsu
country: Japan
facility: Seirei Mikatahara General Hospital
state: Shizuoka
city: Suntohgun, Nagaizumityo
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Utsunomiya
country: Japan
facility: Tochigi Cancer Center
state: Tochigi
city: Shinjuku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyusyu Cancer Center
city: Yamagata
country: Japan
facility: Yamagata University Hospital
Study officials:
affiliation: National Cancer Center Hospital East, Department of Hepatobiliary Pancreatic Oncology
name: Masafumi Ikeda, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shizuoka Cancer Center Hospital
name: Katsuhiko Uesaka, M.D., Ph.D.
role: STUDY_CHAIR
References:
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.
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.