UMIN-CTR Clinical Trial

Public title

A tolerability study in Japan of Oxaliplatin, fluorouracil, and l-leucovorin for patients with stage II/III colon cancer

Acronym

A tolerability study in Japan of OxaliplatIN, fluorouracil, and l-leucovorin for patients with stage II/III colon cancer(JFMC41-1001-C2: JOIN Trial)

Scientific Title

A tolerability study in Japan of Oxaliplatin, fluorouracil, and l-leucovorin for patients with stage II/III colon cancer

Scientific Title:Acronym

A tolerability study in Japan of OxaliplatIN, fluorouracil, and l-leucovorin for patients with stage II/III colon cancer(JFMC41-1001-C2: JOIN Trial)

Region

Japan

Condition

StageII/III colon cancer

Classification by specialty

Gastroenterology	Hematology and clinical oncology	Gastrointestinal surgery
Hepato-biliary-pancreatic surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To confirm tolerability Oxaliplatin, fluorouracil, and l-leucovorin for Japanese patients with stage II/III colon cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

The frequency of allergies, anaphylaxis, and peripheral sensory neuropathy lasting for 8 days (Grade 3 or 4).

Key secondary outcomes

(1) Disease-free survival.
(2) Relapse-free survival.
(3) Time to treatment failure.
(4) Overall survival.
(5) Adverse events.
(6) Peripheral neuropathy.
(7) Completion rate.
(8) Relative dose intensity.
(9) Relationship between lymph node metastasis and prognosis.
(10) Exploration of predictors of the prognosis and adverse events (Additional study).

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

Gene

Interventions/Control_1

L-OHP85mg/m2,l-LV200mg/m2, 5FU400mg/m2(bolus),and 5FU2400mg/m2(infusion)

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) Stage II/Stage III, histologically confirmed colon cancer.
2) Curability A.
3) Chemotherapy starting within 7 weeks after resection and 2 weeks after registration.
4) Age of 20 years or older.
5) Performance status of 0-2.
6) No prior chemotherapy, immunotherapy, or radiation.
7) Adequate organ function:
i) neutrophil count >1,500 /mm3,
ii) platelet count >=100,000/mm3,
iii) serum creatinine <=1.25 times the ULN,
iv) total bilirubin <2 times the ULN,
v) AST, ALT <2 times the ULN, and
vi) CEA <10 ng/mL.
8) Pregnancy test: (-).
9) Women who will not become pregnant.
10) Written informed consent.

Key exclusion criteria

1) Women who are pregnant or breast-feeding.
2) Women who are planning to become pregnant.
3) Appendix cancer.
4) Patients with a history of malignancy.
5) Participating in another clinical trial within 30 days.
6) Peripheral sensory neuropathy >= Grade 1.
7) Insulin-treated diabetic patients.
8) Uncontrolled congestive heart failure, angina pectoris, hypertension, and arrhythmia.
9) Patients with a history of significant neurological or mental illness.
10) Active infectious disease.
11) Other patients who are unfit for the study as determined by the attending physician.

Target sample size

800

Name of lead principal investigator

1st name	Takayuki
Middle name
Last name	Yoshino

Organization

National Cancer Center Hospital East

Division name

Endoscopy & Gastrointestinal Oncology

Zip code

277-8577

Address

6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan

TEL

04-7133-1111

Email

tyoshino@east.ncc.go.jp

Name of contact person

1st name	Yukari
Middle name
Last name	Kawamura

Organization

Japanese Foundation for Multidisciplinary Treatment of Cancer

Division name

Office

Zip code

136-0071

Address

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

Yakult Honsha Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Japanese Foundation for Multidisciplinary Treatment of Cancer

Address

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

Tel

03-5627-7594

Email

jfmc-dc@jfmc.or.jp

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

2010

Year

11

Month

01

Day

URL releasing protocol

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

Publication of results

Published

URL related to results and publications

https://doi.org/10.1007/s00280-019-03957-5

Number of participants that the trial has enrolled

882

Results

The PSN for >=8 days and the incidence of Gr.>=3 AR were 3.3% and 1.7%, respectively. At the onset of PSN, the median total dose of L-OHP and the median number of courses were 672.5mg/m2 and 9, respectively, while the corresponding values were 565.1mg/m2 and 7.5 at the onset of Gr.>=3 AR. Gr.3PSN appeared to gradually recover from 5.8% to 1.1%, 0.5%, and 0.2% at 12mths, 24mths and 36mths after enrollment, respectively. However, Gr.1 or Gr.2 PSNs after 3yrs follow-up were observed in 21.0% of patients.

Results date posted

2019

Year

09

Month

26

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Baseline patient characteristics were as follows: median age, 64 years; male, 53.8%; PS 0, 93.8%; stage II/IIIA/IIIB/IIIC by TNM Classification, 7th edition, 18.5/7.3/52.5/21.6%; and lymph nodes examined, <12 / >12/ unknown: 17.2/82.5/0.2%, respectively.

Participant flow

Between November 2010 and March 2012, 882 patients were enrolled at 198 institutions. Among these 882 patients, 11 were ineligible. Of the remaining 871 eligible patients, 864 patients (98%) for whom the treatment status was fixed with a median follow-up of 3 years as of October 30, 2015 via an electronic data capture system with central monitoring, were included in the efficacy analysis. Among these 871 eligible patients, 9 did not start the study treatment, and 14 did not receive the correct initial dosage at their physician's discretion. These 23 patients were excluded from the safety analysis by central monitoring. Of the remaining 848 patients, 828(94%) patients for whom the treatment status was fixed by April 30, 2013, were included in the safety analysis.

Adverse events

The only grade >=3 AE occurring in more than 10 % of the patients was neutropenia, which was observed in 28.7 %. However, the incidence of febrile neutropenia was 0.4 %. There was only one case of grade 3 interstitial pneumonitis, and there were no treatment-related deaths.

Outcome measures

Three-year DFS, RFS, and OS in the overall efficacy population were 76.1% (95%CI: 73.02 to 78.80), 77.3% (95% CI: 74.34 to 80.02), and 92.7% (95%CI: 90.69 to 94.26), respectively. Favorable 3-year DFS, RFS, and OS were 92.1, 92.8, and 97.4% in stage II patients, while these were 76.4, 77.9, and 93.8% in stage IIIA/B; and 61.6, 62.7, and 85.9% in stage IIIC, respectively. The main recurrent sites were liver (7.6%), lung (7.3%), and lymph nodes (5.2%).

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2010

Year

10

Month

04

Day

Date of IRB

2010

Year

09

Month

09

Day

Anticipated trial start date

2010

Year

11

Month

01

Day

Last follow-up date

2015

Year

03

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

10

Month

26

Day

Last modified on

2019

Year

09

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005318