UMIN-CTR Clinical Trial

Public title

An Open-Label Randomized Phase III Study of Capecitabine(6 months) versus Capecitabine(12 months) as Adjuvant Chemotherapy for Stage III(Dukes'C) Colon Cancer Patients.

Acronym

An Open-Label Randomized Phase III Study of Capecitabine(6 months) versus Capecitabine(12 months) as Adjuvant Chemotherapy for Stage III(Dukes'C)Colon Cancer Patients.
(JFMC37-0801)

Scientific Title

An Open-Label Randomized Phase III Study of Capecitabine(6 months) versus Capecitabine(12 months) as Adjuvant Chemotherapy for Stage III(Dukes'C) Colon Cancer Patients.

Scientific Title:Acronym

An Open-Label Randomized Phase III Study of Capecitabine(6 months) versus Capecitabine(12 months) as Adjuvant Chemotherapy for Stage III(Dukes'C)Colon Cancer Patients.
(JFMC37-0801)

Region

Japan

Condition

Colon cancer

Classification by specialty

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To demonstrate that capecitabine(12 months) is superior to capecitabine(6 months) in terms of desease free survival(DFS) in chemotherapy-naive Stage III(Dukes'C)colon cancer patients.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

Disease free survival

Key secondary outcomes

Relapse free survival, Overall survival, 2-year disease-free survival rate, Adverse events, Individual dose intensity, Health related quality of life, Pharmacoeconomics

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Capecitabine (Xeloda) is administered orally as tablets, 1250 mg/m2 twice daily for 14 days followed by a 7-days resting period without treatment, as an intermittent therapy in a 3-weeks cycle for 8 treatment cycles (6 months).

Interventions/Control_2

Capecitabine (Xeloda) is administered orally as tablets, 1250 mg/m2 twice daily for 14 -days followed by a 7-days resting period without treatment, as an intermittent therapy in a 3-weeks cycle for 16 treatment cycles (12 months).

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

80

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Histologically confirmed Colorectal adenocarcinoma
2) Histological Stage III Colon, Rectosigmoid cancer
3) Curative resection with D2 or more lymph node dissection
4) Resection of histological curability A was performed
5) Performance status(ECOG): 0 or 1
6) No prior chemotherapy and radiotherapy
7) Oral intake is possible
8) Sufficient organ functions
WBC >= 3,000/mm3, <12,000/mm3
Hemoglobin >= 9.0g/dL
Platelet >= 90,000/mm3
Serum creatinine <= 1.5xULN
Total bilirubin <= 1.5 xULN
AST,ALT <= 2.5xULN
ALP <= 2.5xULN
9) Creatinine clearance >50mL/min
10) Chemotherapy will be started within 8 weeks from operation
11) Written informed consent

Key exclusion criteria

1) Pregnant or nursing
2) Medical history of allergy or hypersensitivity reactions to fluoropyrimidines
3) The past of the internal organ transplant
4) Serious coexisting illness
a; severe pulmonary dysfunction
b; ileus or colon dysfunction
c; uncontrolled diabetes mellitus
d; liver cirrhosis
e; uncontrolled hypertension
f; history of myocardial infarction, unstable angina within 6 months prior to the registration
5) Active synchronous or metachronous malignancy other than carcinoma in situ
6) Uncontrollable infectious disease
7) Not suitable for participating in the study for any other reason

Target sample size

1200

Name of lead principal investigator

1st name
Middle name
Last name	Naohiro Tomita

Organization

Hyogo College of Medicine

Division name

Department of Surgery

Zip code

Address

1-1, Mukogawa , Nishinomiya City, Hyogo, 663-8501, Japan

TEL

Email

Name of contact person

1st name
Middle name
Last name	Japanese Foundation for Multidisciplinary Treatment of Cancer

Organization

Japanese Foundation for Multidisciplinary Treatment of Cancer

Division name

Office

Zip code

Address

TaniBuilding3F, 1-28-6, kameido, koutou-ku, Tokyo, 136-0071, Japan

TEL

03-5627-7594

Homepage URL

http://www.jfmc.or.jp/

Email

jfmc-dc@jfmc.or.jp

Institute

Japanese Foundation for Multidisciplinary Treatment of Cancer

Institute

Department

Personal name

Organization

Japanese Foundation for Multidisciplinary Treatment of Cancer

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2008

Year

09

Month

10

Day

URL releasing protocol

http://www.jfmc.or.jp/wp-content/uploads/2015/01/jfmc37_0801.pdf

Publication of results

Published

URL related to results and publications

https://doi.org/10.1038/s41416-019-0410-0

Number of participants that the trial has enrolled

1306

Results

The 5-year DFS
6M:65.3% (95% CI: 61.45-68.79)
12M:68.7% (95% CI: 64.92-72.10)
HR 0.858 (90% CI: 0.732-1.004; p = 0.0549)

The 5-year RFS
6M:69.3% (95% CI: 65.57-72.69)
12M:74.1% (95% CI: 70.53-77.32)
HR 0.796 (90% CI: 0.670-0.945; p = 0.0143)

The 5-year OS
6M:83.2% (95% CI: 80.07-85.87)
12M:87.6% (95% CI: 84.73-89.89)
HR 0.727 (90% CI: 0.575-0.919; p = 0.0124)

Results date posted

2019

Year

03

Month

18

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Postoperative colorectal cancer patients who meet the criteria described in the study plan.

Participant flow

Excluding two patients due to registration error, 1304 patients were randomly assigned to the two groups: 654 patients in the 6M group (control arm) and 650 patients in the 12M group (study arm).Eight and 17 patients were ineligible and 11 and 12 did not receive the protocol treatment in the 6M and 12M groups, respectively.

Adverse events

The overall incidence rate of AEs was 91.7% and 94.7% in the 6M and 12M groups, respectively. The most common AE was hand-foot syndrome (HFS). Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS than the standard 6-month treatment; meanwhile, while toxicities even after 12-month capecitabine were clinically acceptable.

Outcome measures

DFS:disease free survival
RFS:relapse free survival
OS:overall survival
Safety
IDI:Individual Dose Intensity

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2008

Year

06

Month

12

Day

Date of IRB

2008

Year

06

Month

12

Day

Anticipated trial start date

2008

Year

09

Month

01

Day

Last follow-up date

2014

Year

12

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2008

Year

09

Month

10

Day

Last modified on

2019

Year

03

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001662