UMIN-CTR Clinical Trial

Basic information
Public title	A phase 2 study of combination neoadjuvant chemotherapy with gemcitabine S-1 and leucovorin in patients with borderline and locally advanced pancreatic cancer
Acronym	NAC-GSL
Scientific Title	A phase 2 study of combination neoadjuvant chemotherapy with gemcitabine S-1 and leucovorin in patients with borderline and locally advanced pancreatic cancer
Scientific Title:Acronym	NAC-GSL
Region	Japan

Condition
Condition	Borderline and Locally advanced pancreatic cancer
Classification by specialty	Hepato-biliary-pancreatic medicine
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and safety of GEM+S-1+LV combination therapy for borderline and locally advanced pancreatic cancers
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	R0 resection rate
Key secondary outcomes	Resection rate, Progression free survival, Overall survival, Response rate, Disease control rate, Adverse events, Intra-operative complication, Post-operative complication, Operative time, Postoperative length of stay

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	GEM+S-1+LV combination therapy GEM:1,000mg/m2, day1 S-1:80mg/day(BSA<1.25/m2) 100mg/day(1.25/m2=<BSA<1.5/m2) 120mg/day(BSA=>1.5/m2), day1-7 LV:50mg/day, day1-7 repeated every 2weeks.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients with pancreatic cancer without prior treatment 2) Patients with pathologically proven pancreatic cancer 3) Borderline and locally advanced pancreatic cancer 4) Without distant metastasis 5) Patients with Eastern Chemotherapy Oncology Group(ECOG) performance status of 0-2 6) Patients of age >= 20 years 7) Patients who can eat 8) Patients have an adequate organ function defined as white cell count >= 3,000/mm3, neutophils >=1,500/mm3, platelet count >= 100,000/mm3, hemoglobin >= 9g/dl, total bilirubin <= 3 times the upper limit of normal, AST and ALT <= 5 times the upper limit of normal, creatinine <= 1.5 times the upper limit of normal 9) Estimated survival > 2months 10) Written informed consent is required from all patients.
Key exclusion criteria	1) Patients with systolic blood pressure < 100mmHg 2) Patients with an active concomitant infection 3) Patients with digestive ulcer or gastrointestinal bleeding, severe heart or renal disease 4) Patients with an active pulmonary fibrosis or interstitial pneumonia 5) Patients with severe diarrhea 6) Pregnant, lactating female and patients of reproductive potential who did not use effective contraception 7) Patients with uncontrollable massive pleural effusion or massive ascites 8) Patients with an active concomitant malignancy 9) Inappropriate patients for entry on this study in the judgement of the investigator
Target sample size	24

Research contact person
Name of lead principal investigator	1st name Yousuke Middle name Last name Nakai
Organization	The University of Tokyo
Division name	Gastroenterology
Zip code	113-8655
Address	7-3-1, Hongo Bunkyo-ku Tokyo
TEL	03-3815-5411
Email	ynakai-tky@umin.ac.jp

Public contact
Name of contact person	1st name Kei Middle name Last name Saito
Organization	The University of Tokyo Hospital
Division name	Department of Gastroenterology
Zip code	113-8655
Address	7-3-1, Hongo Bunkyo-ku Tokyo
TEL	03-3815-5411
Homepage URL
Email	kesaitou-nii@umin.ac.jp

Sponsor
Institute	The University of Tokyo Hospital
Institute
Department

Funding Source
Organization	The University of Tokyo Hospital
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	The University of Tokyo Hospital
Address	7-3-1, Hongo Bunkyo-ku Tokyo
Tel	03-5800-8743
Email	crctky-office@umin.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2013 Year 12 Month 04 Day

Related information
URL releasing protocol	https://link.springer.com/article/10.1007%2Fs12032-018-1158-8
Publication of results	Published

Result
URL related to results and publications	https://link.springer.com/article/10.1007%2Fs12032-018-1158-8
Number of participants that the trial has enrolled	24
Results	Twenty-four patients with PC (21 BR and 3 LA) were enrolled. Response rate and disease control rate of NAC were 17.4 and 87.0%. Grade 3 and 4 toxicities involved neutropenia (34.8%), anorexia (17.4%), and mucositis (17.4%). Serum CA19-9 level decreased by 52.2%. Resection rate was 60.9% after the median of 4 cycles and R0 resection rate was 76.5% in patients undergoing laparotomy. NAC-GSL is a feasible treatment option for BR and LAPC.
Results date posted	2019 Year 06 Month 09 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Of 24 patients enrolled between January 2014 and December 2016, 23 patients were eligible for the study protocol. One patient was excluded from the analysis because active concomitant malignancy was diagnosed prior to the introduction of GSL therapy.
Participant flow	Two cases did not complete NAC: one case withdrew consent and one had traumatic cerebral hemorrhage unrelated to NAC. In addition, 4 cases were diagnosed as unresectable during NAC due to disease progression: 2 distant metastasis and 2 local disease progression.17 cases (70.8%) who were considered as surgical candidates.
Adverse events	Grade 3 and 4 adverse events developed in 8 cases (34.8%). The major grade 3 and 4 adverse events were neutropenia, anorexia, and mucositis, which were observed in 4 cases (17.4%). Adverse events were manageable after dose reduction and discontinuation of GSL therapy due to toxicity was unnecessary. No toxicity-related death was observed during the preoperative period.
Outcome measures	An R0 resection rate of 76.5% was achieved after the median of 4 courses of NAC-GSL.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 12 Month 02 Day
Date of IRB	2013 Year 11 Month 25 Day
Anticipated trial start date	2013 Year 12 Month 04 Day
Last follow-up date	2018 Year 05 Month 18 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2013 Year 12 Month 03 Day
Last modified on	2019 Year 06 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014596

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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