Clinical Trials List
Protocol NumberONO-4538-43/CA209577
NCT Number(ClinicalTrials.gov Identfier)NCT02743494
Completed
2017-01-18 - 2020-04-30
Phase III
Terminated3
ICD-9150.8
Malignant neoplasm of other specified part of esophagus
A Randomized, Multicenter, Double Blind, Phase III Study of Nivolumab or Placebo in Subjects with Resected Lower Esophageal, or Gastroesophageal Junction Cancer
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
ONO Pharmaceutical Co., Ltd. /Bristol-Myers Squibb Company
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yau-Lin Tseng Division of Thoracic Surgery
- Nai-Jung Chiang Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- 劉奕廷 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Co-Principal Investigator
- Chun-Ru Chien Division of Radiation Therapy
- Ming-Yu Lien Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Yu-Sen Lin Division of Thoracic Surgery
- 林昱森醫師 Division of Thoracic Surgery
- 方信元 Division of Thoracic Surgery
- 王耀慶醫師 Division of Radiation Therapy
- Yao-Ching Wang Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- 黃培銘 Division of General Surgery
- Kun-Huei Yeh Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- JANG-MING LEE Division of Thoracic Surgery
- JHE-CYUAN GUO Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Resected Esophageal, or Gastroesophageal Junction Cancer
Objectives
Primary objectives:
This study has co-primary objectives:
To compare OS of nivolumab versus placebo in subjects with resected EC or GEJ cancer.
To compare DFS of nivolumab versus placebo in subjects with resected EC or GEJ cancer.
Secondary objectives:
To evaluate 1, 2, and 3 year survival rates of nivolumab versus placebo in subjects with resected EC or GEJ
cancer.
Test Drug
Nivolumab
Active Ingredient
Nivolumab
Dosage Form
Solution for Injection
Dosage
10mg/mL, 10mL/vial
Endpoints
Primary endpoints:
Overall survival and DFS are co-primary endpoints.
Overall Survival is time between the date of randomization and the date of death. For subjects without
documentation of death, OS will be censored on the last date the subject was known to be alive.
Disease-Free Survival is time between randomization date and first date of recurrence or death, whichever occurs
first. Recurrence is defined as the appearance of one or more new lesions, which can be local, regional, or distant in
location from the primary resected site (by imaging or pathology whichever comes first). All deaths without prior
recurrence will be included as DFS event - regardless of cause or of how long it has been since the last known
disease evaluation. For subjects who remain alive and without recurrence, DFS will be censored on the date of last
evaluable disease assessment.
Secondary endpoint: Overall survival rate at 1, 2, and 3 years is defined as the probability that a subject is alive at
1, 2, and 3 years, respectively, following randomization.
Overall survival and DFS are co-primary endpoints.
Overall Survival is time between the date of randomization and the date of death. For subjects without
documentation of death, OS will be censored on the last date the subject was known to be alive.
Disease-Free Survival is time between randomization date and first date of recurrence or death, whichever occurs
first. Recurrence is defined as the appearance of one or more new lesions, which can be local, regional, or distant in
location from the primary resected site (by imaging or pathology whichever comes first). All deaths without prior
recurrence will be included as DFS event - regardless of cause or of how long it has been since the last known
disease evaluation. For subjects who remain alive and without recurrence, DFS will be censored on the date of last
evaluable disease assessment.
Secondary endpoint: Overall survival rate at 1, 2, and 3 years is defined as the probability that a subject is alive at
1, 2, and 3 years, respectively, following randomization.
Inclution Criteria
Key Inclusion Criteria
All subjects must have Stage II or Stage III (per AJCC 7th edition) carcinoma of the esophagus or
gastroesophageal junction and have histologically confirmed predominant adenocarcinoma or squamous cell
carcinoma esophageal or gastroesophageal junction cancer at the time of initial diagnosis.
Subjects must complete pre-operative chemoradiotherapy followed by surgery prior to randomization. Platinum
based chemotherapy should be used. Chemotherapy and radiation regimens can be followed as local standards
of care per NCCN or ESMO guidelines.
Subject must have complete resection (R0), have been surgically rendered free of disease with negative margins
on resected specimens. Subject must have residual pathologic disease, i.e. non-pathologic complete response
(non-pCR) of their EC or GEJ, with at least ypN1 or ypT1 listed in the pathology report of resected specimens.
The pathology reports of detectable lesion(s) confirming malignancy must be reviewed, dated, and signed by
the investigator prior to randomization.
Complete resection must be performed in a window of 4-12 weeks prior to randomization.
ECOG performance status score of 0 or 1.
All subjects must have disease-free status documented by a complete physical examination and imaging studies
within 4 weeks prior to randomization. Imaging studies must include CT scan of chest, and abdomen.
Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be
randomized, a subject must have a PD-L1 expression classification (1%, < 1% or indeterminate) as
determined by the central lab. If insufficient tumor tissue content is provided for analysis, acquisition of
additional archived tumor tissue (block and /or slides) for the biomarker analysis is required.
All subjects must have Stage II or Stage III (per AJCC 7th edition) carcinoma of the esophagus or
gastroesophageal junction and have histologically confirmed predominant adenocarcinoma or squamous cell
carcinoma esophageal or gastroesophageal junction cancer at the time of initial diagnosis.
Subjects must complete pre-operative chemoradiotherapy followed by surgery prior to randomization. Platinum
based chemotherapy should be used. Chemotherapy and radiation regimens can be followed as local standards
of care per NCCN or ESMO guidelines.
Subject must have complete resection (R0), have been surgically rendered free of disease with negative margins
on resected specimens. Subject must have residual pathologic disease, i.e. non-pathologic complete response
(non-pCR) of their EC or GEJ, with at least ypN1 or ypT1 listed in the pathology report of resected specimens.
The pathology reports of detectable lesion(s) confirming malignancy must be reviewed, dated, and signed by
the investigator prior to randomization.
Complete resection must be performed in a window of 4-12 weeks prior to randomization.
ECOG performance status score of 0 or 1.
All subjects must have disease-free status documented by a complete physical examination and imaging studies
within 4 weeks prior to randomization. Imaging studies must include CT scan of chest, and abdomen.
Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be
randomized, a subject must have a PD-L1 expression classification (1%, < 1% or indeterminate) as
determined by the central lab. If insufficient tumor tissue content is provided for analysis, acquisition of
additional archived tumor tissue (block and /or slides) for the biomarker analysis is required.
Exclusion Criteria
Key exclusion criteria
Subjects with cervical esophageal carcinoma. Location of tumor as it relates to eligibility can be discussed with
BMS medical monitor.
Subjects who do not receive concurrent CRT prior to surgery. Subjects who only receive chemotherapy or only
radiation prior to surgery are not eligible.
Subjects with Stage IV resectable disease.
Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not
requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are
permitted to enroll.
Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical
steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of
active autoimmune disease.
Subjects with cervical esophageal carcinoma. Location of tumor as it relates to eligibility can be discussed with
BMS medical monitor.
Subjects who do not receive concurrent CRT prior to surgery. Subjects who only receive chemotherapy or only
radiation prior to surgery are not eligible.
Subjects with Stage IV resectable disease.
Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not
requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are
permitted to enroll.
Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical
steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of
active autoimmune disease.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
760 participants
