UMIN-CTR Clinical Trial

Public title

A Randomized, Multicenter, Phase III Study to Compare 6 Months of either 5-Fluorouracil / l-leucovorin plus Oxaliplatin (mFOLFOX6) or Capecitabine plus Oxaliplatin (XELOX) with 3 Months of either mFOLFOX6 or XELOX as Adjuvant Chemotherapy in Patients with Completely Resected high-risk Stage II Colon Cancer

Acronym

Adjuvant Chemotherapy for colon cancer with HIgh EVidencE in high-risk stage II
(JFMC48-1301-C4: ACHIEVE-2 Trial)

Scientific Title

A Randomized, Multicenter, Phase III Study to Compare 6 Months of either 5-Fluorouracil / l-leucovorin plus Oxaliplatin (mFOLFOX6) or Capecitabine plus Oxaliplatin (XELOX) with 3 Months of either mFOLFOX6 or XELOX as Adjuvant Chemotherapy in Patients with Completely Resected high-risk Stage II Colon Cancer

Scientific Title:Acronym

Adjuvant Chemotherapy for colon cancer with HIgh EVidencE in high-risk stage II
(JFMC48-1301-C4: ACHIEVE-2 Trial)

Region

Japan

Condition

high-risk stage II colon cancer (including rectosigmoid cancer)

Classification by specialty

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

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate the non-inferiority of treatment with modified FOLFOX6 or XELOX for 3 months as adjuvant chemotherapy to 6 months of mFOLFOX6/ XELOX in terms of disease-free survival by IDEA pooled analysis for curatively resected high-risk stage II colon cancer (including rectosigmoid cancer).

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

Disease-free survival 1*.
*DFS1 is defined as relapse or death by IDEA

Key secondary outcomes

(1) Disease-free survival 2*.
*DFS2 is defined as relapse, second cancer or death
(2) Time to treatment failure
(3) Overall survival
(4) Adverse events
(5) Completion rate
(6) Relative dose intensity
(7) Relationship between risk factors for recurrence and prognosis
(8) Follow-up of peripheral sensory neuropathy and palmar-plantar erythrodysesthesia syndrome

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Standard Arm (six months)

(1)mFOLFOX6 (12 courses)
L-OHP 85mg/m2
l-LV 200mg/m2
5-FU 400mg/m2 (bolus)
5-FU 2400mg/m2 (infusion)
every 2weeks

(2)XELOX (8 courses)
L-OHP 130mg/m2 day1
Capacitabine 2000 or 1500*mg/m2 day1 - 15(bid)
every 3 weeks
*For patients with CCr<=50mL/min or age >=70

Interventions/Control_2

Test Arm (three months)

(1)mFOLFOX6 (6 courses)
L-OHP 85mg/m2
l-LV 200mg/m2
5-FU 400mg/m2 (bolus)
5-FU 2400mg/m2 (infusion)
every 2weeks

(2)XELOX (4 courses)
L-OHP 130mg/m2 day1
Capacitabine 2000 or 1500*mg/m2 day1 - 15(bid)
every 3 weeks
*For patients with CCr<=50mL/min or age>= 70

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) Histologically confirmed adenocarcinoma of the colon.
(2) Predominantly located in the cecum, colon, or rectosigmoid region based on the findings from surgery and/or surgical specimen.
(3) D2 or D3 lymph nodes resection.
(4) Curability A surgery (no residual tumor visible to macroscopically and/or microscopically).
(5) Stage II (SS/A/SE/SI/AI, N0, M0) (cf. The Japanese Classification of Colorectal Carcinoma, 7th edition, revised version) with at least one of the following risk factors for recurrence.
a) T4(SE/SI/AI)
b) bowel obstruction
c) bowel perforation/ penetration
d) less than 12 lymph nodes examined
e) poorly differentiated adenocarcinoma, signet ring cell adenocarcinoma or mucinous adenocarcinoma
f) vascular or lymphatic invasion (ly or v)
(6) Registration within 8 weeks after resection and chemotherapy starting within 2 weeks after registration.
(7) Age >= 20 years.
(8) ECOG performance status of 0-1.
(9) Body surface area (DuBois) <=2.2 m2.
(10) No prior chemotherapy, immunotherapy, or radiation therapy.
(11) Adequate organ function:
1) neutrophil count >=1,500/mm3
2) platelet count >=100,000/mm3
3) serum creatinine <=1.5 times the ULN
4) CCr >=30mL/min
5) total bilirubin <=2.0 mg/dL
6) AST and ALT <=100 IU/L
7) CEA <=10 ng/mL
(12) Written informed consent.

Key exclusion criteria

(1) Cancer of the appendix.
(2) Past history of malignancy. (When there is the unrecurred period of 5 or more years, the intramucosal carcinoma [stomach cancer, colorectal cancer, esophagus cancer] by which recovery excision was performed endoscopically, the uterine cervical cancer, the basal cell carcinoma of the skin, and squamous cell carcinoma of the skin by which curative excision was performed can be enrolled.)
(3) Women who are pregnant or breast-feeding.
(4) Women who may become pregnant and fertile men.
(5) Participation in another clinical trial within 30 days before registration.
(6) Existing grade 1 or more peripheral sensory neuropathy.
(7) Uncontrolled diabetes mellitus (including insulin therapy).
(8) Uncontrolled congestive heart failure, angina pectoris, hypertension, and/or arrhythmia.
(9) Continuous systemic steroid therapy (oral or intravenous administration).
(10) A history and/or current evidence of significant neurological and/or mental illness.
(11) Active infectious disease (including known active hepatitis B virus infection, hepatitis C virus infection and human immunodeficiency virus).
(12) Known dihydropyrimidine dehydrogenase (DPD) deficiency.
(13) A history of allergy to 5-FU, l-LV, oxaliplatin, and/or capecitabine.
(14) Prior chemotherapy including oxaliplatin.
(15) Other reasons for being unfit for the study as determined by the attending physician.

Target sample size

500

Name of lead principal investigator

1st name
Middle name
Last name	Yoshihiko Maehara(1), Atsushi Ohtsu (2),Takayuki Yoshino (3)

Organization

Graduate School of Medical Sciences
Kyushu University (1),
National Cancer Center Hospital East(2),(3)

Division name

Department of Surgery and Science(1),Department of Gastrointestinal Oncology(3)

Zip code

Address

3-1-1 Maidashi, Higashi-ku, Fukuoka City, FUKUOKA, 812-8585, Japan (1), 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan(2), (3)

TEL

092-642-5461(1)04-7133-1111(2)(3)

Email

jfmc48@jfmc.or.jp

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

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

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

2014

Year

01

Month

31

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2013

Year

10

Month

25

Day

Date of IRB

Anticipated trial start date

2014

Year

02

Month

12

Day

Last follow-up date

2024

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

01

Month

31

Day

Last modified on

2018

Year

02

Month

23

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015216