UMIN-CTR Clinical Trial

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

Colorectal Cancer

Classification by specialty

Gastroenterology

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

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

Primary outcomes

Progression-Free Survival

Key secondary outcomes

Response rate
Overall survival
Adverse events

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Kyushu Study group of Clinical Cancer

Institute

Department

Personal name

Organization

Taiho Pharmaceutical Co., LTD

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2016

Year

12

Month

13

Day

URL releasing protocol

https://jrct.niph.go.jp/re/reports/detail/5490

Publication of results

Published

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

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 related information

Registered date

2016

Year

12

Month

13

Day

Last modified on

2021

Year

08

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029010