| Eligibility |
Inclusion Criteria:
- Be at least 16 years of age;
- Histologic diagnosis of resected Stages IIIB/IIIC/ IV melanoma, with no evidence of
disease clinically and radiologically, and negative surgical margins. All melanomas
regardless of primary site of disease will be allowed;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given
to control the cancer) must have been completed at least 4 weeks before study drug
administration, and all adverse events have either returned to baseline or stabilized;
- Prior treated brain or meningeal metastases must be without magnetic resonance imaging
(MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of
systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before
study drug administration;
- Prior systemic radiation therapy must have been completed at least 4 weeks before
study drug administration. Prior focal radiotherapy completed at least 2 weeks before
study drug administration. No radiopharmaceuticals (strontium, samarium) within 8
weeks before study drug administration;
- Immunosuppressive doses of systemic medications, such as steroids or absorbed topical
steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2
weeks before study drug administration;
- Completed nitrosourea treatment at least 6 weeks before administration of any study
drug;
- Prior surgery that required general anesthesia must be completed at least 4 weeks
before study drug administration. Surgery requiring local/epidural anesthesia must be
completed at least 72 hours before study drug administration and subjects should be
recovered;
- Screening laboratory values must meet the following criteria:
white blood cells (WBCs) = 2000 cells/µL
- neutrophils = 1500 cells/µL
- platelets = 100 x 103/µL
- hemoglobin = 9.0 g/dL
- serum creatinine = 2 mg/dL
- AST = 2.5 x upper limit of normal (ULN) without, and = 5 x ULN with hepatic metastasis
- ALT = 2.5 x ULN without, and = 5 x ULN with hepatic metastasis
- bilirubin = 2 x ULN (except subjects with Gilbert's syndrome, who must have total
bilirubin < 3.0 mg/dL)
- Females of childbearing potential must:
- use appropriate method(s) of contraception. WOCBP should use an adequate method to
avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo
five half-lives) after the last dose of investigational drug.
- Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
start of nivolumab.
- For female subjects to be considered as not having childbearing potential, they must
meet 1 or more of the following criteria:
- postmenopausal for at least 24 consecutive months;
- surgically sterile (ie, have had a hysterectomy or bilateral oophorectomy);
- females with irregular menstrual periods and/or on hormone replacement therapy must
have a documented serum follicle stimulating hormone level > 35 mIU/mL;
- Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year Men receiving nivolumab and who are sexually
active with WOCBP will be instructed to adhere to contraception for a period of 31
weeks after the last dose of investigational product Women who are not of childbearing
potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men
do not require contraception.
- Subject must have read, understood, and provided written informed consent and HIPAA
authorization after the nature of the study has been fully explained; and
- Willing to adhere to the study visit schedule and the prohibitions and restrictions
specified in this protocol.
Exclusion Criteria:
- Subjects who fulfill any of the following conditions at Screening will not be eligible
for admission into the study:
- History of severe hypersensitivity reactions to other mAbs;
- Prior non-melanoma malignancy active within the previous 2 years except for locally
curable cancers that have been apparently cured, such as basal or squamous cell skin
cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or
breast;
- Subjects with any active autoimmune disease (Appendix 3) or a documented history of
autoimmune disease, or history of syndrome that required systemic steroids or
immunosuppressive medications, except for subjects with vitiligo or resolved childhood
asthma/atopy;
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS);
- Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus
ribonucleic acid (HCV RNA) indicating active or chronic infection;
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or
any other antibody targeting T cell co-stimulation pathways);
- Concurrent medical condition requiring the use of immunosuppressive medications, or
immunosuppressive doses of systemic or absorbable topical corticosteroids;
- Underlying medical condition (eg, a condition associated with diarrhea) that, in the
Investigator's opinion, would make the administration of either study drug or both
study drugs hazardous to the subject or obscure the interpretation of toxicity
determination or adverse events;
- Pregnant or nursing; or
- Current participation in another clinical study involving treatment with medications,
radiation or surgery, or prior participation in this study.
- Patients are excluded if they have active brain metastases or leptomeningeal
metastases. Subjects with brain metastases are eligible if metastases have been
treated and there is no magnetic resonance imaging (MRI) evidence of progression for
[lowest minimum is 4 weeks or more] after treatment is complete and within 28 days
prior to the first dose of nivolumab administration. There must also be no requirement
for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone
equivalents) for at least 2 weeks prior to study drug administration.
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab
combinations, drugs with a predisposition to hepatoxicity should be used with caution in
patients treated with nivolumab-containing regimen.
- Allergies and Adverse Drug Reaction
1. History of allergy to study drug components
2. History of severe hypersensitivity reaction to any monoclonal antibody
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