Fully resected (Stage IIIb/c or Stage IV) melanoma & Adjuvant therapy
Conditions
Interventions
The medical interventions for this trial include both Nivolumab and Ipilimumab.
All compounds will be supplied by the Sponsor Company with exception of the
placebo. (Should be sourced by investigati
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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. • 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. The Primary purpose of Revised Protocol 06 is to extend the collection of Overall Survival (OS) data for approximatively 5 additional years. In addition, data associated with the primary, secondary, and exploratory efficacy outcomes (eg. melanoma recurrence data, data on development of new primary melanomas and non-melanoma cancers, subsequent anti-cancer therapies) will continue to be collected on Case Report Forms. Study-drug-related serious adverse events (SAEs) will continue to be collected, whereas follow-up surveillance imaging assessments, plasma biomarker samples, and the EQ-5D questionnaire will no longer be required during extended follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Netherlands
Outcome results
None listed