Gastric Cancer
Conditions
Keywords
Gastric Cancer, Gastrointestinal Diseases, Gastrointestinal Neoplasms, First Line Treatment, Antineoplastic Agents
Brief summary
The purpose of this trial is to evaluate the efficacy of TAS-118 plus Oxaliplatin compared with S-1 plus Cisplatin in overall survival in patients with advanced gastric cancer.
Interventions
DRUGTAS-118 plus Oxaliplatin
Sponsors
Yakult Honsha Co., LTD
Taiho Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients who are diagnosed as gastric cancer. * No prior treatment for gastric cancer. * Negative or unknown for HER2 testing. * ECOG performance status of 0 or 1. Key
Exclusion criteria
* Unmanageable diarrhea. * Current peripheral sensory neuropathy or paresthesia. * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | A survival follow-up was required every 12 weeks from the date of randomization to the date of death from any cause, whichever came first, assessed up to 38 months. | The primary endpoint was OS, which was defined as the time from the date of randomization to the date of death from any cause. Surviving patients were censored at the cutoff date or last contact date if lost to follow-up, or upon withdrawal of consent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | A radiographic imaging examination using CT or MRI was repeated every 6 weeks. Tumor assessments were performed from the date of randomization to the date of disease progression or death from any cause, whichever came first. | PFS was defined as the time from the date of randomization to the date of disease progression (assessed by each investigator) or death from any cause, whichever came first. |
| Time to Treatment Failure | From the date of randomization to the date of the last administration of the study drug. | TTF was defined as the time from the date of randomization to the date of the last administration of the study drug. Patients on study treatment were censored at the date of the last administration or the cutoff date, whichever came earlier. |
| Overall Response Rate | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months. | ORR was defined as the proportion of patients with the best unconfirmed overall response of complete response (CR) or partial response (PR) in patients with measurable lesions |
| Disease Control Rate | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months. | DCR was defined as the proportion of patients with CR, PR, or stable disease in patients with measurable lesions. |
Countries
Japan, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAS-118/Oxaliplatin TAS-118 plus Oxaliplatin
L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met. | 347 |
| S-1/Cisplatin S-1 plus Cisplatin
CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met. | 334 |
| Total | 681 |
Baseline characteristics
| Characteristic | TAS-118/Oxaliplatin | S-1/Cisplatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 146 Participants | 140 Participants | 286 Participants |
| Age, Categorical Between 18 and 65 years | 201 Participants | 194 Participants | 395 Participants |
| Age, Continuous | 62.0 years | 62.0 years | 62.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 347 Participants | 334 Participants | 681 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 347 Participants | 334 Participants | 681 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 221 participants | 212 participants | 433 participants |
| Region of Enrollment South Korea | 126 participants | 122 participants | 248 participants |
| Sex: Female, Male Female | 96 Participants | 116 Participants | 212 Participants |
| Sex: Female, Male Male | 251 Participants | 218 Participants | 469 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 352 | 8 / 348 |
| other Total, other adverse events | 344 / 352 | 328 / 348 |
| serious Total, serious adverse events | 155 / 352 | 159 / 348 |
Outcome results
Primary
Overall Survival
The primary endpoint was OS, which was defined as the time from the date of randomization to the date of death from any cause. Surviving patients were censored at the cutoff date or last contact date if lost to follow-up, or upon withdrawal of consent.
Time frame: A survival follow-up was required every 12 weeks from the date of randomization to the date of death from any cause, whichever came first, assessed up to 38 months.
Population: Full Analysis Set (FAS)：Patients in AT population who have advanced gastric cancer at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAS-118/Oxaliplatin | Overall Survival | 16.0 Months |
| S-1/Cisplatin | Overall Survival | 15.1 Months |
p-value: 0.03995% CI: [0.69, 0.99]Log Rank
Secondary
Disease Control Rate
DCR was defined as the proportion of patients with CR, PR, or stable disease in patients with measurable lesions.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months.
Population: TR Evaluable Population：
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAS-118/Oxaliplatin | Disease Control Rate | 197 Participants |
| S-1/Cisplatin | Disease Control Rate | 187 Participants |
p-value: 0.092Fisher Exact
Secondary
Overall Response Rate
ORR was defined as the proportion of patients with the best unconfirmed overall response of complete response (CR) or partial response (PR) in patients with measurable lesions
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months.
Population: Tumor Response (TR) Evaluable Population： Patients in FAS population presenting measurable lesions (at least one target lesion), evaluated for tumor responses at least once during treatment with the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAS-118/Oxaliplatin | Overall Response Rate | 155 Participants |
| S-1/Cisplatin | Overall Response Rate | 106 Participants |
p-value: <0.001Fisher Exact
Secondary
Progression-free Survival
PFS was defined as the time from the date of randomization to the date of disease progression (assessed by each investigator) or death from any cause, whichever came first.
Time frame: A radiographic imaging examination using CT or MRI was repeated every 6 weeks. Tumor assessments were performed from the date of randomization to the date of disease progression or death from any cause, whichever came first.
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAS-118/Oxaliplatin | Progression-free Survival | 7.1 Months |
| S-1/Cisplatin | Progression-free Survival | 6.4 Months |
p-value: 0.004595% CI: [0.66, 0.93]Log Rank
Secondary
Time to Treatment Failure
TTF was defined as the time from the date of randomization to the date of the last administration of the study drug. Patients on study treatment were censored at the date of the last administration or the cutoff date, whichever came earlier.
Time frame: From the date of randomization to the date of the last administration of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAS-118/Oxaliplatin | Time to Treatment Failure | 6.1 Months |
| S-1/Cisplatin | Time to Treatment Failure | 5.3 Months |
p-value: 0.01195% CI: [0.7, 0.96]Log Rank