UMIN-CTR Clinical Trial

Basic information
Public title	A phase III randomized study of capecitabine as adjuvant chemotherapy versus observation in breast cancer with pathologic residual tumors after preoperative chemotherapy(JBCRG-04)
Acronym	JBCRG-04(CREATE-X)
Scientific Title	A phase III randomized study of capecitabine as adjuvant chemotherapy versus observation in breast cancer with pathologic residual tumors after preoperative chemotherapy(JBCRG-04)
Scientific Title:Acronym	JBCRG-04(CREATE-X)
Region	Japan Asia(except Japan)

Condition
Condition	Breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	This study is designed to investigate the efficacy and safety of capecitabine, as a postoperative adjuvant chemotherapy, for breast cancer patients who have pathologic residual cancer cells after the preoperative chemotherapy. In addition, the cost-effectiveness of capecitabine is to be investigated.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Disease free survival
Key secondary outcomes	Overall survival, safety, cost-effectiveness, Time to recurrence, time to death

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	chemotherapy (capecitabine)
Interventions/Control_2	Standard therapy (hormone therapy, radiotherapy)
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	75 years-old >
Gender	Female
Key inclusion criteria	1. Female patient with primary, infiltrative breast cancer who has been diagnosed on a histological basis. 2. Stage I-IIIB at the first diagnosis and underwent curative resection. 3. The patient was non-pCR after preoperative chemotherapy including anthracycline agents; that is, she had undergone primary tumor resection and pathologically confirmed to have residual cancer cells. The previously adminstered preoperative chemotherapy must have involved at least four cycles of anthracycline agents. However, even if Anthracycline regimen is shorter than 4 courses, the following regimen can be registered. - FEC 3 courses (EPI>=100mg/m2)+Docetaxel 3 courses - FEC 3 courses+TC (Docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2) 3 courses - TC 3 courses+FEC 3 courses - TC only over 4 courses 4. The patient has been confirmed to be HER2 negative. etc. 5. The patient is aged 20 to 74 6. The patient's general performance status is 0 to 1. 7. The patient must have no carry-over of efficacy from any previous treatment. 8. The patient has maintained sufficient organ function to permit valid evaluation. 9. The patient must have no adverse drug reactions of grade 2 or higher carried over from previous treatment. 10. The ptient's creatinine clearance is higher than 50 mL/min 11. The patient has personally given written, informed consent to participate in this study.
Key exclusion criteria	1. The patient is considered to require postoperative chemotherapy other than capecitabine. 2. The patient has previously been treated with oral 5-FU agents (however, previous treatment with iv 5-FU is acceptable). 3. The patient has either simultaneous or non-simultaneous bilateral breast cancer. 4. The Patients has or has a history of other malignancies or synchronic multiple cancers. However, lesions corresponding to carcinoma in situ or intramucosal carcinoma healed by topical therapy are eligible. 5. The patient is pregnant, has the potential and/or wishes to become pregnant, or is breastfeeding. 6. The patient has previously had an organ transplant. 7. The patient shows hypersensitivity to fluoropyrimidine agents; has previously suffered severe adverse drug reactions with fluoropyrimidine agents; or has a history of serious hypersensitivity to LHRH analogs, tamoxifen, letrozole, anastrozole, and/or exemestane. 8. The patient is currently suffering from serious complications or associated disorders, such as malignant hypertension, congestive heart failure, coronary failure, arrhythmias requiring treatment, infectious diseases, and/or hemorrhagic tendency, and/or has suffered a myocardial infarction within the previous 6 months. 9. The patient has a fever, and there is the possibility that she has an infection. 10. The patient has been shown to have metastasis to other organs. 11. The patient requires treatment for epilepsy and/or central nervous system disorders. 12. The patient is currently being treated for, or has a history of, psychiatric disease. 13. It would be difficult to orally administer drugs to the patient, and/or she suffers from functional insufficiency of the upper gastrointestinal tract and/or malabsorption syndrome. 14. For any other reason, the investigator or sub-investigator has judged the patient to be ineligible for participation.
Target sample size	900

Research contact person
Name of lead principal investigator	1st name Norikzau Middle name Last name Masuda
Organization	Osaka National Hospital
Division name	Department of Surgery (Breast Oncology)
Zip code	540-0006
Address	1-14, 2-chome Hoenzaka, Chuou-ku, Osaka-city, Osaka
TEL	06-6942-1331
Email	nmasuda@alpha.ocn.ne.jp

Public contact
Name of contact person	1st name Jun Middle name Last name Fukase
Organization	JBCRG
Division name	Head office
Zip code	103-0016
Address	9-4-3F, Nihonbashikoamicho, Chuo-ku, Tokyo, Japan
TEL	03-6264-8873
Homepage URL	https://www.jbcrg.jp/
Email	office@jbcrg.jp

Sponsor
Institute	JBCRG (Japan Breast Cancer Research Group) KBCS(Korean Breast Cancer Society) KCSG(Korean Cancer Study Group)
Institute
Department

Funding Source
Organization	ACRO (Advanced Clinical Research Organization),JBCRG (Japan Breast Cancer Research Group)
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	JBCRG
Address	9-4 Nihonbashikoamicho, Chuo-ku, Tokyo, Japan
Tel	03-6264-8873
Email	office@jbcrg.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

(北海道)北海道大学病院Hokkaido University Hospital/ 北海道がんセンターHokkaido Cancer Center (青森県)弘前市立病院Hirosaki Municipal Hospital (岩手県)岩手医科大学附属病院Iwate Medical University (宮城県)宮城県立がんセンターMiyagi Cancer Center (群馬県)群馬県立がんセンターGunma Prefectural Cancer Center (茨城県)土浦協同病院Tsuchiura Kyodo General Hospital (栃木県)自治医科大学附属病院Jichi Medical University Hospital (埼玉県)さいたま赤十字病院Saitama Red Cross Hospital (東京都)多摩総合医療センターTokyo Metropolitan Tama Medical Center/ 東京都立駒込病院Tokyo Metropolitan Komagome Hospital/ 東京共済病院Tokyo Kyosai Hospital/ 国立がんセンター中央病院National Cancer Center Hospital/ 東京慈恵会医科大学附属病院The Jikei University Hospital/ 虎ノ門病院Toranomon Hospital/ 順天堂大学医学部附属順天堂病院Juntendo University Hospital (神奈川県)東海大学医学部付属病院Tokai University Hospital/ 聖マリアンナ医科大学病院St. Marianna University School of Medicine Hospital/ 神奈川県立がんセンターKanagawa Cancer Center (石川県)金沢大学医学部附属病院Kanazawa University Hospital (福井県)福井赤十字病院Fukui Red Cross Hospital (長野県)信州大学医学部附属病院Shinshu University School of Medicine/ 飯田市立病院Iida Municipal Hospital (山梨県)山梨県立中央病院Yamanashi Prefectural Central Hospital (愛知県)愛知県がんセンター中央病院Aichi Cancer Center Hospital/ 名古屋医療センターNagoya Medical Center/ 名古屋市立東部医療センター東市民病院Nagoya City East Medical Center/ 一宮市立市民病院Ichinomiya Municipal Hospital/ 名古屋市立大学病院Nagoya City University Hospital (京都府) 京都大学医学部附属病院Kyoto University Hospital/ 京都民医連中央Kyoto Miniren Chuo Hospital (大阪府)大阪医療センターOsaka National Hospital/ 堺市立総合医療センターSakai City Medical Center/ りんくう総合医療センターRinku General Medical Center/ 八尾市立病院Yao Municipal Hospital/大阪労災病院Osaka Rosai Hospital/大阪赤十字病院Osaka Red Cross Hospital/ 大阪警察病院Osaka Police Hospital/大阪市立大学医学部附属病院Osaka City University Hospital/関西医科大学附属枚方病院Kansai Medical University Hirakata Hospital/相原病院Aihara Hospital/ 大阪大学医学部附属病院Osaka University Hospital (奈良県)市立奈良病院Nara City Hospital/ 奈良県立医科大学付属病院Nara Medical University Hospital (和歌山県)公立那賀病院Naga Hospital (兵庫県)兵庫県立がんセンターHyogo Cancer Center/ 兵庫医科大学病院Hyogo College of Medicine (岡山県)岡山大学病院Okayama University Hospital (広島県)広島市立安佐市民病院Hiroshima City Asa Citizens Hospital/ 広島市立広島市民病院Hiroshima City Hiroshima Citizens Hospital/ 済生会広島病院Saiseikai Hiroshima Hospital/ JA広島総合病院Hiroshima General Hospital/ 広島大学病院Hiroshima University Hospital/ 県立広島病院Hiroshima Prefectural Hospital (山口県)山口大学医学部附属病院Yamaguchi University Hospital (島根県)松江赤十字病院Matsue Red Cross Hospital (愛媛県)四国がんセンターShikoku Cancer Center (福岡県)九州がんセンターNational Hospital Organization Kyushu Cancer Center (熊本県)熊本市立熊本市民病院Kumamoto City Hospital (大分県)別府医療センターBeppu Medical Center (鹿児島県)博愛会相良病院Social Medical Corporation Hakuaikai, Sagara Hospital (沖縄県)中頭病院Nakagami Hospital Samsung Medical Center Seoul National University Bundang Hospital Severance Hospital Asan Medical Center Yeungnam University Medical Center National Cancer Center Korea University Anam Hospital Ajou University Hospital Kyungpook National university hospital Chungbuk National University Hospital Soonchunhyang University Hospital Bucheon Inje University Busan Paik hospital Gangnam Severance Hospital Hallym University Kangdong Sacred Heart Hospital Gangneung Asan Hospital Inha University Hospital Seoul National University Hospital Ewha Womans University Mokdong Hospital Hallym University Sacred Heart Hospital Konkuk University Medical Center Soonchunhyang University Hospital Cheonan Inje University Sanggye Paik Hospital

Other administrative information
Date of disclosure of the study information	2007 Year 11 Month 01 Day

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

Result
URL related to results and publications	https://www.nejm.org/doi/full/10.1056/NEJMoa1612645
Number of participants that the trial has enrolled	910
Results	RESULTS: DFS was longer in the capecitabine group than in the control group (74.1% vs. 67.6%). OS was longer in the capecitabine group than in the control group (89.2% vs. 83.6%). CONCLUSIONS: After standard neoadjuvant chemotherapy, the addition of adjuvant capecitabine therapy was safe and effective in prolonging DFS and OS among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing.
Results date posted	2021 Year 08 Month 13 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2017 Year 06 Month 01 Day
Baseline Characteristics	Breast cancer patients who have been pathologically confirmed to have residual cancer cells after the administration of preoperative chemotherapy involving anthracycline agents and the primary tumor resection (non-pCR patients).
Participant flow	Patients were randomly assigned equally to the capecitabine group and the control group (standard therapy) as postsurgical treatment.
Adverse events	The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group.
Outcome measures	Primary endpoint: Disease-free survival (DFS) Secondary endpoints: Overall survival (OS),safety
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2006 Year 10 Month 18 Day
Date of IRB	2006 Year 11 Month 28 Day
Anticipated trial start date	2007 Year 02 Month 01 Day
Last follow-up date	2015 Year 09 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2007 Year 10 Month 06 Day
Last modified on	2021 Year 08 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000989