Esophageal Cancer
Conditions
Brief summary
The purpose of study is to evaluate the efficacy and safety of Nivolumab in unresectable advanced or recurrent esophageal cancer patients who have failed in standard chemotherapies.
Interventions
DRUGNivolumab
DRUGDocetaxel/Paclitaxel
Sponsors
Bristol-Myers Squibb
Ono 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
* Men & women ≥20 years of age * Histologically confirmed unresectable advanced or recurrent esophageal cancer * Refractory to or intolerant of standard therapy * ECOG Performance Status score 0 or 1 * A life expectancy of at least 3 months
Exclusion criteria
* Current or past history of severe hypersensitivity to any other antibody products * Patients with multiple primary cancers * Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment * Patients with active, known or suspected autoimmune disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | (Date of death from any cause - Date of randomization + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | (Earlier date on which either the overall response was assessed as PD or the subject died of any cause - Date of randomization + 1) / 30.4375. | Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE). |
| Duration of Response | (Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause - Date of first assessment of confirmed CR or PR + 1) / 30.4375. | Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE). |
Countries
Denmark, Germany, Italy, Japan, South Korea, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab Arm Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | 210 |
| Active Comparator Arm （Docetaxel/Paclitaxel） Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
OR
Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | 209 |
| Total | 419 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Nivolumab Arm | Active Comparator Arm （Docetaxel/Paclitaxel） | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 98 Participants | 124 Participants | 222 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 85 Participants | 197 Participants |
| Age, Continuous | 64 years | 67 years | 65 years |
| Disease stage : TNM classification II - III | 8 Participants | 13 Participants | 21 Participants |
| Disease stage : TNM classification IV | 94 Participants | 100 Participants | 194 Participants |
| Disease stage : TNM classification unknown | 5 Participants | 7 Participants | 12 Participants |
| ECOG performance status 0 | 101 Participants | 107 Participants | 208 Participants |
| ECOG performance status 1 | 109 Participants | 102 Participants | 211 Participants |
| History of smoking Current | 21 Participants | 30 Participants | 51 Participants |
| History of smoking Former | 159 Participants | 147 Participants | 306 Participants |
| History of smoking Never | 30 Participants | 32 Participants | 62 Participants |
| Number of organs of metastases <=1 | 89 Participants | 91 Participants | 180 Participants |
| Number of organs of metastases >=2 | 121 Participants | 118 Participants | 239 Participants |
| PD-L1 expression <1% | 109 Participants | 107 Participants | 216 Participants |
| PD-L1 expression >=1% | 101 Participants | 102 Participants | 203 Participants |
| PD-L1 expression <10% | 146 Participants | 152 Participants | 298 Participants |
| PD-L1 expression >=10% | 64 Participants | 57 Participants | 121 Participants |
| PD-L1 expression <5% | 136 Participants | 137 Participants | 273 Participants |
| PD-L1 expression >=5% | 74 Participants | 72 Participants | 146 Participants |
| Previous therapies Radiothrapy | 153 Participants | 142 Participants | 295 Participants |
| Previous therapies Surgery | 111 Participants | 94 Participants | 205 Participants |
| Previous therapies Systemic anticancer therapy | 210 Participants | 208 Participants | 418 Participants |
| Race/Ethnicity, Customized Asian | 201 Participants | 200 Participants | 401 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 9 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 201 Participants | 200 Participants | 401 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 | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 31 Participants | 24 Participants | 55 Participants |
| Sex: Female, Male Male | 179 Participants | 185 Participants | 364 Participants |
| Site of metastases Bone | 23 Participants | 25 Participants | 48 Participants |
| Site of metastases Liver | 57 Participants | 54 Participants | 111 Participants |
| Site of metastases Lung | 98 Participants | 92 Participants | 190 Participants |
| Site of metastases Lymph node | 159 Participants | 163 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 209 | 5 / 208 |
| other Total, other adverse events | 185 / 209 | 204 / 208 |
| serious Total, serious adverse events | 68 / 209 | 77 / 208 |
Outcome results
Primary
Overall Survival
Time frame: (Date of death from any cause - Date of randomization + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Arm | Overall Survival | 10.9 months |
| Active Comparator Arm （Docetaxel/Paclitaxel） | Overall Survival | 8.4 months |
Secondary
Duration of Response
Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE).
Time frame: (Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause - Date of first assessment of confirmed CR or PR + 1) / 30.4375.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Arm | Duration of Response | 6.9 months |
| Active Comparator Arm （Docetaxel/Paclitaxel） | Duration of Response | 3.9 months |
Secondary
Progression-free Survival
Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE).
Time frame: (Earlier date on which either the overall response was assessed as PD or the subject died of any cause - Date of randomization + 1) / 30.4375.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Arm | Progression-free Survival | 1.7 months |
| Active Comparator Arm （Docetaxel/Paclitaxel） | Progression-free Survival | 3.4 months |