UMIN-CTR Clinical Trial

Public title

A Phase III Study of Docetaxel plus S-1 versus S-1 Alone in the Treatment of Curatively Resected Stage III Gastric Cancer

Acronym

JACCRO GC-07 (START-2)

Scientific Title

A Phase III Study of Docetaxel plus S-1 versus S-1 Alone in the Treatment of Curatively Resected Stage III Gastric Cancer

Scientific Title:Acronym

JACCRO GC-07 (START-2)

Region

Japan

Condition

Gastric Cancer

Classification by specialty

Gastroenterology	Hematology and clinical oncology	Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To compare the 3-years recurrence free survival, 5-year overall survival, 5-year recurrence free survival and safety of the test arm (docetaxel and S-1) to the control arm (S-1 only) in patients with curatively resected stage III gastric cancer.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Primary outcomes

3-years recurrence free survival rate

Key secondary outcomes

3-years and 5-years overall survival
5-years recurrence free survival
time to treatment failure
adverse events

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

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1st Course (S-1 alone): S-1 80mg/m2 d1-14, q3w
2nd to 7th Course (S-1 plus docetaxel):Docetaxel: 40 mg/m2 (1 hour IV infusion) on Day 1 of each cycle
S-1: S-1 dosage is dependent upon BSA calculation on Days 1-14 of each cycle. No treatment on Days 15 through 21 of each cycle.Cycles repeated every 3weeks.
After 7th Course, S-1 alone continued until 1 year.

Interventions/Control_2

S-1: S-1 dosage is dependent upon BSA calculation on Days 1 through 28 of each cycle,no treatment on Days 29 through 42 of each cycle, cycles repeated until 1 year.

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 proven gastric cancer of IIIA, IIIB or IIIC (Histologically Common Type)
2. D2 lymph-node dissection with R0 surgery (with the result of no residual tumor)
3. No hepatic, peritoneal, or distant metastasis; no tumor cells in peritoneal fluid on cytologic analysis
4. Age 20 to 80 years.
5. No previous treatment for cancer except for the initial gastric resection for the primary lesion.
6. ECOG performance status 0 or 1.
7. Within 42 days after gastric resection and adequate self-supported nutritional intake.
8. Hgb>9.0 g/dL, WBC 4000-12,000/mm3, ANC> 1500/mm3, platelets> 100,000/mm3
9. Creatinine< 1.2 mg/dL, Creatinine clearance> 50mL/min
10. Total bilirubin< 1.5 X UNL
11. AST (SGOT) and ALT (SGPT)< 100 IU/L
12. Subjects must have fully recovered from surgical damage
13. Written informed consent

Key exclusion criteria

1. Active double cancer (except focal cancer in adenoma of colorectal cancer and carcinoma in situ of cervical cancer) and/or past history of other cancer.
2. Patients with severe postoperative complication (severe postoperative infections, anastomotic leakage, gastrointestinal bleeding).
3. Patients with severe complication (intestinal paralysis, intestinal obstruction, interstitial pneumonitis, pulmonary fibrosis, severe diabetes, uncontrolled hypertension, heart failure, renal failure, liver cirrhosis, liver failure, etc.).
4. Patient with active infectious desease.
5. Patient with positive HBs antigen or positive HCV antibody.
6. Definite contraindications for the use of corticosteroids.
7. History of hypersensitivity to fluoropyrimidines, docetaxel, or medications formulated with polysorbate 80, other severe drug induced allergy or .
8. History of allergy of both iodine and gadolinium.
9. Patient is taking flucytosine.
10. Pregnancy or lactation women, women with suspected pregnancy or men with willing to get pregnant.
11. Patient with psychosis or psychotic symptoms and judged to be difficult to determine participating clinical trial.
12. Any subject judged by the investigator to be unfit for any reason to participate in the study.

Target sample size

1100

Name of lead principal investigator

1st name	Yasuhiro
Middle name
Last name	Kodera

Organization

Nagoya University

Division name

Department of Digestive Surgery

Zip code

466-8560

Address

65, Tsurumai, Showa-ku, Nagoya, Japan

TEL

052-741-2111

Email

ykodera@med.nagoya-u.ac.jp

Name of contact person

1st name	Masashi
Middle name
Last name	Fujii

Organization

Japan Clinical Cancer Reseach Organization (JACCRO)

Division name

Research Office

Zip code

101-0051

Address

6F Jimbocho Kyowa Bldg, 1-64-3 Kanda-Jimbocho, Chiyoda-ku, Tokyo

TEL

03-6811-0433

Homepage URL

Email

gc07.dc@jaccro.or.jp

Institute

Japan Clinical Cancer Reseach Organization (JACCRO)

Institute

Department

Personal name

Organization

Japan Clinical Cancer Reseach Organization (JACCRO)

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Japan Clinical Cancer Reseach Organization (JACCRO)

Address

6F Jimbocho Kyowa Bldg, 1-64-3 Kanda-Jimbocho, Chiyoda-ku, Tokyo

Tel

03-6811-0433

Email

jaccro@jaccro.or.jp

Secondary IDs

YES

Study ID_1

jRCTs041180146

Org. issuing International ID_1

Japan Registry of Clinical Trials

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

名古屋大学医学部附属病院（愛知県）ほか、JACCRO参加施設

Date of disclosure of the study information

2013

Year

04

Month

01

Day

URL releasing protocol

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180146

Publication of results

Published

URL related to results and publications

https://doi.org/10.1007/s10120-023-01419-9

Number of participants that the trial has enrolled

951

Results

Postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection.

Results date posted

2025

Year

05

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The median age was 70 years (range, 37-87), 642 patients (70.4%) were male and 270 patients (29.6%) were female. ECOG performance status was 0 in 789 patients (86.5%) and 1 in 123 patients (13.5%). 296 patients (32.5%) were Stage IIIA, 317 patients (34.8%) were Stage IIIB and 299 patients (32.8%) were Stage IIIC.

Participant flow

Of 915 randomly assigned patients, 912 patients (n=454 in S-1 plus docetaxel group; n=459 in S-1 group) were intention-to-treat (ITT) analysis.

Adverse events

One patient in the S-1 group died of respiratory failure, which was considered to be an adverse drug reaction. Hospitalization as a result of
severe adverse events occurred in 76 patients (17%; 95% CI 13% to 20%) in the S-1 plus docetaxel group and 67 patients (15%; 95% CI 11% to 18%) in the S-1 group.
The most common grade 3 or 4 AEs were hematologic events, such as leukopenia (22.4% in S-1 plus docetaxel group; 2.7% in S-1 group), neutropenia (39.2% in S-1 plus docetaxel group; 16.4% in S-1 group), anorexia (13.6% in S-1 plus docetaxel group; 12.0% in S-1 group) and febrile neutropenia (5.7% in S-1 plus docetaxel group; 0.4% in S-1 group).

Outcome measures

The second interim analysis of Relapse-free survival (RFS) demonstrated the superiority of the S-1 plus docetaxel group (HR, 0.632; 99.99% CI, 0.400 to 0.998; P,.001), with a 3-year RFS of 66% (95% CI, 59% to 73%) in the S-1 plus docetaxel group and 50% (95% CI, 41% to 58%) in the S-1 group.
The 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (HR, 0.715; 95% CI, 0.587 to 0.871; P, 0.0008).
The 3-year Overall Survival (OS) rate of 77.7% in the S-1 plus docetaxel group was significantly superior to 71.2% in the S-1 group (HR, 0.742; 95% CI, 0.596 to 0.925; p, 0.0076).
The 5-year RFS of 59.8% in the S-1/docetaxel group was significantly superior to 50.6% in the S-1 group (HR, 0.726; 95% CI, 0.599-0.879; p, 0.0010) and the 5y OS was 67.9% in the S-1/docetaxel group and that of S-1 group was 60.3%, respectively (HR, 0.752; 95% CI, 0.613 to 0.922; p, 0.0059), confirming the significant improving effect on the survival of the patient.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

03

Month

30

Day

Date of IRB

2013

Year

03

Month

06

Day

Anticipated trial start date

2013

Year

04

Month

01

Day

Last follow-up date

2022

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

03

Month

28

Day

Last modified on

2025

Year

05

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012099