A study to assess the efficacy and safety of Nivolumab and Ipilimumab in the treatment of patients with Stage III or IV Melanoma. Patients will then receive Nivolumab until the end of the study.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 615

Inclusion Criteria

a) Subjects with histologically-confirmed unresectable stage III or stage IV melanoma as per AJCC 2010 staging system, including mucosal and ocular melanoma, regardless of BRAF mutation status
b) Subjects are included if they are newly diagnosed with advanced/metastatic disease and have not received prior systemic treatment for their advanced disease.
Note: Prior adjuvant or neoadjuvant melanoma therapy (including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, such as anti-CD-137) is permitted if the therapy was used in the adjuvant or neoadjuvant setting but not in the metastatic setting. These drugs must be discontinued 6 months prior to study entry. All AEs related to prior adjuvant or neoadjuvant therapy must have either returned to baseline, and eligible patients must not have experienced severe or life-threatening irAEs except those that are unlikely to reoccur with standard countermeasures (eg, hormone replacement after adrenal crisis).
c) Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 2 weeks after treatment is complete and within 6 weeks prior to first dose of study drug administration. (If MRI is contraindicated, CT scan is acceptable). There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (> 10 mg/day prednisone equivalents) for at least
2 weeks prior to study drug administration.
i) Subjects are eligible if they have previously untreated brain metastases and are neurologically asymptomatic (This criterion is restricted to the investigators who have treated at least 3 patients with nivolumab plus ipilimumab combination regimen):
(1) No clinical requirement for local intervention (surgery, radiosurgery, corticosteroid therapy) or other systemic therapy.
(2) Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have received systemic corticosteroid therapy in the 14 days prior to beginning protocol therapy.
ii) If patients had been previously treated and then developed asymptomatic progression (This criterion with details below is restricted to the investigators who have treated at least 3 patients with nivolumab plus ipilimumab combination regimen)
(1) Prior stereotactic radiotherapy (SRT) and prior excision of up to 3 melanoma brain metastases is permitted if there has been complete recovery, with no neurologic sequelae.
(2) Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable.
(3) Any prior surgery or radiotherapy must have occurred at least 6 weeks before the start of dosing for this study.
d) ECOG PS 0-1
e) ECOG PS of 2 (This criterion is restricted to investigators who have treated at least 3 patients with nivolumab plus ipilimumab combination regimen)
f) Tissue tumor (archival or recent acquisition) must be available (block or a minimum of 10 unstained slides of FFPE tissue) for correlative studies.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 308
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 307

Exclusion Criteria

a) leptomeningeal metastases.
b) As of Amendment 04, this criterion is no longer applicable
c) Subjects previously treated with SRT > 3 lesions in the brain
d) Brain lesion > 3 cm
e) History of carcinomatous meningitis (lumbar puncture is not required)
f) Subjects with 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.
g) Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
h) All toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, or peripheral neuropathy must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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