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.
- Conditions
- Fully resected (Stage IIIb/c or Stage IV) melanoma & Adjuvant therapy10040900
- Registration Number
- NL-OMON55473
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
Key Inclusion Criteria:
• At least 15 years of age
Except: where local regulations and/or institutional policies do not allow for
subjects < 18 years of age (pediatric population) to participate. For those
sites, the eligible subject population is >= 18 years of age.
• All subjects must be either Stage IIIb/c or Stage IV American Joint
Committee on Cancer (AJCC) Melanoma Staging (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 usually have
clinically detectable lymph nodes that are confirmed as malignant on the
pathology report and/or ulcerated primary lesions.
Subjects who are *N2c* classification with 2-3 metastatic nodes and in transit
metastases/satellites without metastatic nodes, or, *N3*classification with any
*T* and 4+ metastatic nodes, or matted nodes, or in transit
metastases/satellites with metastatic nodes are eligible. The pathology report
for both Stage IIIb and IIIc 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 in
the setting of Stage IIIb/c or Stage IV 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.
Key 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 or equivalent) or other
immunosuppressive medications within 14 days of randomizationstudy drug
administration. 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. and except for prior adjuvant interferon
(see qualifier below). 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.
i) Prior treatment with adjuvant interferon is allowed if completed >= 6 months
prior to randomization.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary:<br /><br>•To compare the efficacy, as measured by recurrence free survival (RFS),<br /><br>provided by nivolumab versus ipilimumab in subjects with completely resected<br /><br>Stage IIIb/c or Stage IV NED melanoma who are at high-risk for recurrence.<br /><br><br /><br>The Primary purpose of Revised Protocol 06 is to extend the collection of<br /><br>Overall Survival (OS) data for approximatively 5 additional years. In<br /><br>addition, data associated with the primary, secondary, and exploratory efficacy<br /><br>outcomes (eg. melanoma recurrence data, data on development of new primary<br /><br>melanomas and non-melanoma cancers, subsequent anti-cancer therapies) will<br /><br>continue to be collected on Case Report Forms. Study-drug-related serious<br /><br>adverse events (SAEs) will continue to be collected, whereas follow-up<br /><br>surveillance imaging assessments, plasma biomarker samples, and the EQ-5D<br /><br>questionnaire will no longer be required during extended follow-up.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary:<br /><br><br /><br>•To compare the overall survival of nivolumab vs ipilimumab in subjects with<br /><br>completely resected Stage IIIb/c or Stage IV NED melanoma who are at high risk<br /><br>for recurrence;<br /><br>•To assess the overall safety and tolerability of nivolumab and ipilimumab in<br /><br>subjects with completely resected Stage IIIb/c or Stage IV NED melanoma who are<br /><br>at high risk for recurrence;<br /><br>•To evaluate whether PD-L1 expression is a predictive biomarker for RFS;<br /><br>•To evaluate the Health Related Quality of Life (HRQoL) as assessed by European<br /><br>Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30.</p><br>