UMIN-CTR Clinical Trial

Basic information
Public title	A Phase 2 study of concurrent combination therapy of TFTD (TAS-102) and bevacizumab in patients of more than 70 years of age with unresectable, advanced/recurrent colorectal cancer (KSCC 1602)
Acronym	A Phase 2 study of concurrent combination therapy of TFTD (TAS-102) and bevacizumab in patients of more than 70 years of age with unresectable, advanced/recurrent colorectal cancer (KSCC 1602)
Scientific Title	A Phase 2 study of concurrent combination therapy of TFTD (TAS-102) and bevacizumab in patients of more than 70 years of age with unresectable, advanced/recurrent colorectal cancer (KSCC 1602)
Scientific Title:Acronym	A Phase 2 study of concurrent combination therapy of TFTD (TAS-102) and bevacizumab in patients of more than 70 years of age with unresectable, advanced/recurrent colorectal cancer (KSCC 1602)
Region	Japan

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

Objectives
Narrative objectives1	We evaluate exploratory efficacy and safety of 1st line combination therapy of TFTD (TAS-102) and bevacizumab in patients of more than 70 years of age with unresectable advanced/recurrent colorectal cancer.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Progression-Free Survival
Key secondary outcomes	Response rate Overall survival Adverse events

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	TFTD 35 mg/m2, po, bid at day 1-5 and day 8-12 and bevacizumab 5mg/kg, iv, every 2 weeks are concurrently administered. The administration is continued until the meeting of discontinuation criteria as 1 course of 28 days.
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 providing the written informed consent. 2) Patients are >=70 years of age (age at the time of enrollment) 3) Patients with colorectal cancer (excluding appendiceal cancer) pathologically diagnosed. 4) Unresectable colorectal cancer and chemotherapy was not performed as pre-treatment (recurrent patients under adjuvant therapy and within 6 months after adjuvant therapy excluding adjuvant therapy for pathological stage II - III are ineligible) 5) Patients with any of the following: (1) Patients who the standard therapy is possible, but does not enforce the standard therapy by the consultation of investigator and patient (fit) (2) Patients who cannot be received the same standard treatment as a general young people, but can be received some kind of treatment (vulnerable). 6) Performance Status (ECOG) 0 or 1 7) Patients capable of treatment with oral medicine 8) Patients have measurable lesion according to RECIST version 1.1 criteria by trunk part contract-enhanced CT within 28 days before enrollment 9) Patients with sufficient organ function 10) He/she can accept contraception by an appropriate method from the study drug administration to 6 months after final administration. 11) The patient has no severe dysfunction of major organs (bone marrow, liver, kidneys, heart, lungs, etc.) and the patient's laboratory results from up to 14 days prior to enrollment fall within the criteria i) WBC <=12,000/mm3 ii) Neutrophil >=1,500/mm3 iii) Platelet >=100,000/mm3 iv) Hemoglobin >=8.0g/dL v) Total bilirubin <=1.5mg/dL vi) AST, ALT <=100IU/L vii) Albumin >=2.5g/dL viii) Serum creatinine <=1.5mg/dL ix) Creatinine clearance >=60mL/min
Key exclusion criteria	1) Serious drug-induced hypersensitivity (especially, platinum formulation, 5-FU, TFTD) 2) Patients received palliative operation (it is eligible at 28 days after the operation with the intestinal anastomosis, at 14 days after colostomy) 3) Patients with active infectious disorder 4) Patients with uncontrollable hypertension. 5) Patients with under treatment by continuous use of insulin or with complication of uncontrollable diabetes mellitus 6) Patients with cardiac disorder such as congestive heart failure, angina to need medication, transmural myocardial infarction definitely observed in ECG, clinically apparent valvular disease, symptomatic coronary disease, uncontrollable arrhythmia, anamnesis of myocardial infarction that developed within the past 12 months. 7) Patients with severe pulmonary disorder such as interstitial pneumonia, pulmonary fibrosis, severe emphysema. 8) Patients with mental disorder or with anamnesis of central nervous system disorder. 9) Patients who have the fresh bleeding from gastrointestinal tract needing a transfusion repeatedly. 10) Patients who are receiving anticoagulant. 11) Patients with watery stool (>=Grade2) 12) Active double cancer. Synchronous double cancer and metachronous double cancer within a disease-free interval of 5 years. Lesions consistent with carcinoma in situ or intramucosal carcinoma that have been cured by local treatment are not classified as active multiple cancers. 13) Male patients with hope of pregnancy of his partner. 14) Patients with cirrhosis or active hepatitis. 15) Any other patients who are regarded as unsuitable for this study by the investigators
Target sample size	35

Research contact person
Name of lead principal investigator	1st name Eiji Middle name Last name Oki
Organization	Graduate School of Medical Sciences, Kyushu University
Division name	Department of Surgery and Science
Zip code	812-8582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
TEL	092-409-3500
Email	sanae.sakamoto@ks-cc.or.jp

Public contact
Name of contact person	1st name KSCC Middle name Last name Research Secretariat
Organization	Kyushu Study group of Clinical Cancer
Division name	KSCC Research Secretariat
Zip code	812-8582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
TEL	092-409-3500
Homepage URL
Email	sanae.sakamoto@ks-cc.or.jp

Sponsor
Institute	Kyushu Study group of Clinical Cancer
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)

IRB Contact (For public release)
Organization	Kyushu University Ethics Review Board
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
Tel	092-641-1151
Email	byssien@jimu.kyushu-u.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

光晴会病院（長崎県） JCHO人吉医療センター（熊本県） 薫風会佐野病院(兵庫県） 九州大学（福岡県） 国立病院機構九州医療センター（福岡県） 済生会福岡総合病院（福岡県） 製鉄記念八幡病院（福岡県） 社会保険田川病院（福岡県） 久留米大学（福岡県） JCHO久留米総合病院（福岡県） 公立八女総合病院（福岡県） 長崎大学（長崎県） 国立病院機構長崎医療センター（長崎県） 大分県立病院（大分県） 国立病院機構大分医療センター（大分県） 中津市立中津市民病院（大分県） 今給黎総合病院（鹿児島県） 鹿児島厚生連病院（鹿児島県） 鹿児島県立薩南病院（鹿児島県） 松山赤十字病院（愛媛県） 熊本地域医療センター（熊本県） 宗像医師会病院（福岡県） 福岡大学（福岡県） 神戸市立医療センター中央市民病院（兵庫県） 田川市立病院（福岡県） 神戸大学（兵庫県） 九州大学病院別府病院（大分県） JCHO九州病院（福岡県） 佐賀大学（佐賀県） 香川大学（香川県） 柿添病院（長崎県） 飯塚病院（福岡県） 国立病院機構佐賀病院（佐賀県） 熊本大学（熊本県） 広島赤十字・原爆病院（広島県） 伊万里有田共立病院（佐賀県） 中頭病院（沖縄県） 国立病院機構福岡東医療センター（福岡県） 琉球大学（沖縄県） 鹿児島大学（鹿児島県） 豊見城中央病院（沖縄県） 大分中村病院（大分県） 国立病院機構別府医療センター（大分県） 慈愛会今村総合病院（鹿児島県） 公立学校共済組合九州中央病院（福岡県） ハートライフ病院（沖縄県） 済生会川内病院（鹿児島県） 大分赤十字病院（大分県）

Other administrative information
Date of disclosure of the study information	2016 Year 12 Month 13 Day

Related information
URL releasing protocol	https://jrct.niph.go.jp/re/reports/detail/5490
Publication of results	Published

Result
URL related to results and publications	Cancer Med. 2020 Nov 29. doi: 10.1002/cam4.3618. Online ahead of print. PMID: 33249761
Number of participants that the trial has enrolled	39
Results	Primary Endpoint PFS was 8.0 months (80% CI, 6.7-11.2). Secondary Endpoints ORR (CR+PR) was 40.5% (95% confidence interval [CI], 24.8-57.9) median OS was no t reached The AEs which were frequent as grade 3 o r 4 were leucopenia (71.8 % ), neutropenia (48.7 % ), anorexia (12.8 % ), febrile neutropenia (10.3 % ). Major non-hematological AEs were hypertension 8/39 (20.5% ) and Fatigue 4/39 (10.3% ).
Results date posted	2021 Year 08 Month 12 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	In all 39 enrolled patients . The median ag e was 76.0 (rang e: 70-88), and proportions o f ECOG PS 0 and 1 were 24 (61.5% ) and 15(38.5% ), respectively. Ras wild/mutant/no tinvestigated type were 11(28.2% )/23(60.0% )/5(12.5% ). The fit and vulnerable patients are 23/16 respectively.
Participant flow	enrollment period: December 2016-March 13, 2018 Number o f enrolled facilities 18 facilities Tracking period: December 2016-January 31, 2020
Adverse events	Death within 30 days after pro to co l treatment s tart: 0 case Other treatment related death: 1 case (perforation o f co lo n) See Secondary Endpoints as Grade 4 AEs .
Outcome measures	Primary Endpoint PFS : Progression-Free Survival Secondary Endpoints Overall response rate
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 10 Month 05 Day
Date of IRB	2017 Year 02 Month 14 Day
Anticipated trial start date	2016 Year 12 Month 01 Day
Last follow-up date	2020 Year 02 Month 29 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 12 Month 13 Day
Last modified on	2021 Year 08 Month 12 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029010