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

JRCT ID: jRCTs031180128

Registered date:18/02/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: high-risk stage II colon cancer (including rectosigmoid cancer)
• Date of first enrollment: 14/02/2014
• Target sample size: 500
• Study type: Interventional

Intervention(s)

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

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

Outcome(s)

Primary Outcome

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

Secondary Outcome

(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

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Shitara Kohei
• Secondary Sponsor: Maehara Yoshihiko,Ohtsu Atsushi,Yoshino Takayuki
• Source(s) of Monetary Support: Yakult Honsha Co., Ltd
• Secondary ID(s): UMIN000013036