UMIN-CTR Clinical Trial

Basic information
Public title	A randomized, double blind, comparative study of vitamin D3 versus placebo in patients with cancer in gastrointestinal tract to prevent relapse after operation
Acronym	Amaterasu 5
Scientific Title	A randomized, double blind, comparative study of vitamin D3 versus placebo in patients with cancer in gastrointestinal tract to prevent relapse after operation
Scientific Title:Acronym	Amaterasu 5
Region	Japan

Condition
Condition	cancers in gastrointestrinal tract esophageal cancer, gastric cancer, colon cancer
Classification by specialty	Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	1. Targeting on cancers in gastrointestinal tract (esophageal cancer, gastric cancer and colon cancer), we examine relationship between relapse free survival and serum vitamin D concentration/single nuclear polymorphisms of vitamin D receptor 2. By peroral administration of either vitamin D3 (2,000IU) or placebo in double blind manner, vitamin D can prevent relapse and death after primary operation.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	relapse free survival overall survival
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	vitamin D3 supplement
Interventions/Control_2	placebo
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	30 years-old <=
Age-upper limit	90 years-old >
Gender	Male and Female
Key inclusion criteria	1. First operation for cancer of gastrointestinal tract at International University of Health and Welfare hospital 2. Obtained informed consent
Key exclusion criteria	1. Already taking vitamin D supplement or 1,25 vitamin D 2. History of kidney stone 3. Other difficulties judged by the surgeon in charge
Target sample size	1

Research contact person
Name of lead principal investigator	1st name Middle name Last name Mitsuyoshi Urashima
Organization	Jikei University School of Medicine
Division name	Division of Molecular Epidemiology
Zip code
Address	3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461 Japan
TEL
Email

Public contact
Name of contact person	1st name Middle name Last name Emi Suzuki
Organization	Jikei University School of Medicine
Division name	Division of Molecular Epidemiology
Zip code
Address
TEL
Homepage URL
Email	emisuzu@jikei.ac.jp

Sponsor
Institute	International University of Health and Welfare
Institute
Department

Funding Source
Organization	Jikei University School of Medicine
Organization
Division
Category of Funding Organization
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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	2009 Year 06 Month 01 Day

Related information
URL releasing protocol	https://upload.umin.ac.jp/cgi-bin/icdr/ctr_up_reg_f5.cgi
Publication of results	Unpublished

Result
URL related to results and publications	https://upload.umin.ac.jp/cgi-bin/icdr/ctr_up_reg_f5.cgi
Number of participants that the trial has enrolled	417
Results	The 5-year RFS was 77% vs 69%; hazard ratio (HR) for relapse or death, 0.76; 95% CI, 0.50 -1.14; P = 0.18. The 5-year overall survival in the vitamin D and placebo groups was 82% vs. 81%; HR for death, 0.95; 95%CI, 0.57-1.57; P=0.83. In a subgroup of patients with serum 25(OH)D levels between 20 and 40 ng/mL at baseline, the 5-year RFS was 85% vs 71%; HR for relapse or death, 0.46; 95%CI, 0.24-0.86; P=0.02; Pinteraction=0.04.
Results date posted	2019 Year 04 Month 05 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2019 Year 04 Month 10 Day
Baseline Characteristics	The AMATERASU Trial was a randomized, double-blind, placebo-controlled trial at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 patients were excluded after operation.
Participant flow	The patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/day, n=251) or placebo (n=166) from the first postoperative outpatient visit to until the end of the trial.
Adverse events	Fractures occurred in 3 (1.3%) of vitamin D group and 5 (3.4%) of placebo. Urinary stones were in 2 (0.9%) of vitamin D and 0 (0.0%) of placebo.
Outcome measures	The primary outcome was relapse-free survival (RFS) time to relapse or death. The secondary outcome was overall survival time to death from any cause. Subgroups analyzed were baseline serum 25(OH)D level 0 to <20 ng/mL, 20 to 40 ng/mL, and >40 ng/mL; because of small sample size for highest level, interactions were tested only between the low and middle baseline levels.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2009 Year 02 Month 19 Day
Date of IRB	2008 Year 12 Month 25 Day
Anticipated trial start date	2009 Year 10 Month 01 Day
Last follow-up date	2018 Year 01 Month 31 Day
Date of closure to data entry	2018 Year 02 Month 28 Day
Date trial data considered complete	2018 Year 03 Month 07 Day
Date analysis concluded	2018 Year 03 Month 21 Day

Other
Other related information

Management information
Registered date	2009 Year 05 Month 16 Day
Last modified on	2019 Year 04 Month 05 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002412

Research Plan
Registered date	File name
2019/04/05	Protocol + SAP (Original + final + Amandament).pdf

Research case data specifications
Registered date	File name

Research case data
Registered date	File name
2019/04/05	2019.3.22..data repository (1).xlsx

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