UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase I/II Study of S-1 and Oxaliplatin Combined With Radiation for Preoperative Locally Advanced Rectal Carcinoma
Title of the study (Brief title)	JACCRO CC-04 (SHOGUN trial)
Region	Japan

Condition
Condition	Colorectal Cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery Radiology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The purpose of this study is to assess the safety and efficacy of S-1 and oxaliplatin combined with radiation by Phase I/II study. The purpose of this study is as follows, In phase I, to determine the dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD). In phase II, to evaluate the antitumor effect (pCR rate) and the safety.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I,II

Assessment
Primary outcomes	Phase I: to determine the dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) Phase II: pCR rate
Key secondary outcomes	Phase I: pCR rate, R0 resection rate, Down staging rate, Safety Phase II: R0 resection rate, Down staging rate, Local reccurence rate, Disease free survuval, Safety

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	S-1: 40mg/m2 orally twice a day (BID) for 5 days a week at 1st week, 2nd week, 4th week and 5th week. Oxaliplatin: 40-60mg/m2/week intravenously on day 1, 8, 22 and 29. Radiation: Total dose is 50.4Gy (1.8Gy X 28 fractions)
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	80 years-old >=
Gender	Male and Female
Key inclusion criteria	1) The primary tumor is located in the upper rectum above the peritoneal reflection (Ra) or in the lower rectum below the peritoneal reflection (Rb). 2) The main histological type is confirmed to be adenocarcinoma (tub1/tub2). 3) A preoperatively diagnosis of T3 or T4 (any N) tumors on multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) (UICC TNM classification, 7th edition, 2009) . 4) R0 resection is considered feasible. 5) No distant metastasis. 6) Age at the time of obtaining informed consent. Phase I study: 20 years or older to 75 years or younger Phase II study: 20 years or older to 80 years or younger 7) A performance status (Eastern Cooperative Oncology Group, ECOG) of 0 or 1 8) No previous treatment with radiotherapy, chemotherapy, or hormonal therapy. 9) Adequate main organ functions on the basis of data obtained within 14 days before enrollment (examinations performed on the same day of the week 2 weeks before enrollment acceptable) as follows: i) White-cell count >= 4000 /mm3 and <= 12,000/mm3 ii) Neutrophil count >= 2000 /mm3 iii) Platelet count >= 10.0 X 104 /mm3 iv) Hemoglobin >= 9.0 g/dL v) AST (GOT) <= 100 IU/L vi) ALT (GPT) <= 100 IU/L vii) Serum bilirubin <= 1.5 mg/dL viii) Creatinine clearance <= 60.0 mL/min* If creatinine clearance is measured by 24-hour urine collection, that value will be used. If a measured value is unavailable, the estimated creatinine clearance rate will be calculated by using the following Cockcroft-Gault formula. Males: creatinine clearance = body weight X (140; age)/(72 X serum creatinine level) Females: creatinine clearance = 0.85 X {body weight X (140; age)/(72 X serum creatinine level)} 10) The ability to orally ingest food and receive drugs. 11) Written informed consent to participate in the study obtained directly from the patient.
Key exclusion criteria	1) A previous history of serious drug-induced hypersensitivity. 2) A history of radiotherapy of the pelvic cavity. 3) Infection accompanied by a fever of 38.0 degrees C or higher 4) Serious concurrent disease (interstitial pneumonia or pulmonary fibrosis, poorly controlled diabetes mellitus, renal failure, liver failure, etc.). 5) Remarkable electrocardiographic abnormalities or clinically problematic heart disease (heart failure, myocardial infarction, angina pectoris). 6) Sensory neuropathy. 7) Serious diarrhea (watery stool) (however, excluding diarrhea occurring as a defecatory abnormality caused by colorectal cancer). 8) Pleural effusion or ascites that may require puncture to alleviate symptoms. 9) Synchronous multiple primary cancer or metachronous multiple primary cancer with a disease-free survival of 5 years or less (However, patients with early cancer likely to be cured by local treatment will not be excluded.). 10) Women who may (want to) become pregnant, pregnant women, or breast-feeding women. 11) Men who want to have children. 12) Current treatment with flucytosine. 13) In addition, patients who are judged by the responsible study investigator or physician in charge to be inappropriate for enrollment in the study.
Target sample size	45

Research contact person
Name of lead principal investigator	Toshiaki Watanabe
Organization	The University of Tokyo
Division name	Department of Surgical Oncology and Vascular Surgery
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo 1130033, Japan
TEL	03-3815-5411
Email	toshwatanabe@yahoo.co.jp

Public contact
Name of contact person	Masashi Fujii
Organization	Japan Clinical Cancer Research Organization
Division name	Office
Address	1-14-5 Ginza, Chuo-ku, Tokyo 104-0061, Japan
TEL	03-5579-9882
Homepage URL
Email	cc04.dc@jaccro.or.jp

Sponsor
Institute	Japan Clinical Cancer Research Organization
Institute
Department

Funding Source
Organization	Taiho Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

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

Secondary IDs
Secondary IDs	YES
Study ID_1	ClinicalTrials.gov Identifier:NCT01227239
Org. issuing International ID_1	ClinicalTrials.gov Identifier:NCT01227239
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 05 Month 07 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2010 Year 02 Month 27 Day
Anticipated trial start date	2010 Year 09 Month 01 Day
Last follow-up date	2016 Year 08 Month 31 Day
Date of closure to data entry	2016 Year 09 Month 30 Day
Date trial data considered complete	2016 Year 10 Month 31 Day
Date analysis concluded	2016 Year 12 Month 31 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 05 Month 07 Day
Last modified on	2019 Year 03 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020228