Clinical Trials List
Protocol NumberCA209-238
2015-07-01 - 2026-05-29
Phase III
Terminated3
ICD-10C43.9
Malignant melanoma of skin, unspecified
ICD-10D03
Melanoma in situ
A Phase 3, Randomized, Double-blind Study of Adjuvant Immunotherapy with Nivolumab versus Ipilimumab after Complete Resection of Stage IIIb/c or Stage IV Melanoma in Subjects who are at High Risk for Recurrence
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Trial Applicant
BRISTOL-MYERS SQUIBB (TAIWAN) LTD.
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Sponsor
Bristol-Myers Squibb Research and Development
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yu-Li Su Division of Hematology & Oncology
- Chih-Hung Lee Division of Dermatology
- Tai-Jan Chiu Division of Hematology & Oncology
- 黃泰霖 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 藍叡 Division of Others
- 饒坤銘 Division of Hematology & Oncology
- Meng-Jer Hsieh Division of Hematology & Oncology
- 林浩 Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 許致榮 Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Po-Yuan Wu Division of Hematology & Oncology
- 李宗勳 未分科
The Actual Total Number of Participants Enrolled
2 Stop recruiting
Condition/Disease
Melanoma
Objectives
Primary:
• To compare the efficacy, as measured by recurrence free survival (RFS), provided by nivolumab versus
ipilimumab in subjects with completely resected Stage IIIb/c or Stage IV NED melanoma who are at high-risk
for recurrence.
Secondary:
• To compare the overall survival of nivolumab vs ipilimumab in subjects with completely resected Stage IIIb/c
or Stage IV NED melanoma who are at high risk for recurrence;
• To assess the overall safety and tolerability of nivolumab and ipilimumab in subjects with completely resected
Stage IIIb/c or Stage IV NED melanoma who are at high risk for recurrence;
• To evaluate whether PD-L1 expression is a predictive biomarker for RFS;
• To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organisation for Research
and Treatment of Cancer (EORTC) QLQ-C30.
Test Drug
Nivolumab, Ipilimumab
Active Ingredient
Ipilimumab
Nivolumab
Nivolumab
Dosage Form
Injection
Dosage
10mg/ml
5mg/ml
5mg/ml
Endpoints
Primary Endpoint: Recurrence Free Survival in all randomized subjects is the primary endpoint for this study.
Secondary Endpoint: Overall survival is a key secondary endpoint. If RFS superiority is demonstrated, OS will be
tested hierarchically.
Secondary Endpoint: Overall survival is a key secondary endpoint. If RFS superiority is demonstrated, OS will be
tested hierarchically.
Inclution Criteria
• At least 15 years of age
• All subjects must be either Stage IIIb/c or Stage IV AJCC (7th edition) and have histologically confirmed
melanoma that is completely surgically resected in order to be eligible. Subjects must have been surgically
rendered free of disease with negative margins on resected specimens. Please refer to Appendix 1 for
description of AJCC 7th editions of TNM and staging.
If Stage III melanoma (whether Stage IIIb or IIIc) the subjects must have clinically detectable lymph nodes that
are confirmed as malignant on the pathology report and/or ulcerated primary lesions. The pathology report must
be reviewed, signed and dated by the investigator; this process will be confirmed during the IVRS
randomization call. Clinically detectable lymph nodes are defined as:
(1) a palpable node (confirmed as malignant by pathology)
(2) a non-palpable but enlarged lymph node by CT scan (at least 15 mm in short axis) and confirmed as
malignant by pathology
(3) a PET scan positive lymph node of any size confirmed by pathology
(4) evidence of pathologically macrometastatic disease in one or more lymph nodes defined by one or more
foci of melanoma at least 1cm in diameter
If Stage IV melanoma, the pathology report confirming negative margins must be reviewed, dated, and signed
by the investigator prior to randomization.
• Complete resection of Stage III disease that is documented on the surgical and pathology reports or complete
resection of Stage IV disease with margins negative for disease that is documented on the pathology report.
• Complete resection must be performed within 12 weeks prior to randomization
• 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 a CT scan of the neck, chest, abdomen,
pelvis and all known sites of resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if
MRI is contraindicated or if there is no known history of resected brain lesions).
• 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 (positive, negative/or indeterminate) as
determined by a central lab.
• All subjects must be either Stage IIIb/c or Stage IV AJCC (7th edition) and have histologically confirmed
melanoma that is completely surgically resected in order to be eligible. Subjects must have been surgically
rendered free of disease with negative margins on resected specimens. Please refer to Appendix 1 for
description of AJCC 7th editions of TNM and staging.
If Stage III melanoma (whether Stage IIIb or IIIc) the subjects must have clinically detectable lymph nodes that
are confirmed as malignant on the pathology report and/or ulcerated primary lesions. The pathology report must
be reviewed, signed and dated by the investigator; this process will be confirmed during the IVRS
randomization call. Clinically detectable lymph nodes are defined as:
(1) a palpable node (confirmed as malignant by pathology)
(2) a non-palpable but enlarged lymph node by CT scan (at least 15 mm in short axis) and confirmed as
malignant by pathology
(3) a PET scan positive lymph node of any size confirmed by pathology
(4) evidence of pathologically macrometastatic disease in one or more lymph nodes defined by one or more
foci of melanoma at least 1cm in diameter
If Stage IV melanoma, the pathology report confirming negative margins must be reviewed, dated, and signed
by the investigator prior to randomization.
• Complete resection of Stage III disease that is documented on the surgical and pathology reports or complete
resection of Stage IV disease with margins negative for disease that is documented on the pathology report.
• Complete resection must be performed within 12 weeks prior to randomization
• 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 a CT scan of the neck, chest, abdomen,
pelvis and all known sites of resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if
MRI is contraindicated or if there is no known history of resected brain lesions).
• 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 (positive, negative/or indeterminate) as
determined by a central lab.
Exclusion Criteria
• History of ocular/uveal melanoma
• Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, residual
hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
• Subjects with previous non-melanoma malignancies are excluded unless a complete remission was achieved at
least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the
study period (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, in
situ gastric cancer, in situ colon cancers; in situ cervical cancers/dysplasia; or breast carcinoma in situ)
• 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 are permitted in the absence of active autoimmune disease.
• Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or except for adjuvant radiation
therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions. Specifically subjects who
received prior therapy with interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or
checkpoint pathways) are not eligible.
• Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, residual
hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
• Subjects with previous non-melanoma malignancies are excluded unless a complete remission was achieved at
least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the
study period (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, in
situ gastric cancer, in situ colon cancers; in situ cervical cancers/dysplasia; or breast carcinoma in situ)
• 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 are permitted in the absence of active autoimmune disease.
• Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or except for adjuvant radiation
therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions. Specifically subjects who
received prior therapy with interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or
checkpoint pathways) are not eligible.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
800 participants
