| Eligibility |
Inclusion Criteria:
- Age = 19 years
- Histologically or cytologically confirmed mucosal melanoma of head and neck
- Locally advanced and unresectable
- No previous chemotherapy for purpose of palliation
- ECOG performance status of 0~2
- Measurable lesion per RECIST 1.1 criteria
- Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy
of the tissue sample quality for assessment of biomarker status. Repeat samples may be
required if adequate tissue is not provided. Newly obtained endoscopic biopsy
specimens are preferred to archived samples and formalin-fixed, paraffin-embedded
(FFPE) block specimens are preferred to slides.
- Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to
initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be
provided (e.g. inaccessible or subject safety concern) may submit an archived
specimen.
- Collection of an archived tissue sample will also be requested (where available) to
support evaluation of the clinical utility of biomarker assessment in newly obtained
vs. archived tissue samples; however, a subject will not be precluded from
participating in the study if an archived tissue sample is not available for
collection or is otherwise insufficient for analysis.
- Adequate marrow, hepatic, renal and cardiac functions:
Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) = 2.5 x upper limit
of normal (ULN), or AST and ALT = 5 x ULN if liver function abnormalities are due to
underlying malignancy Total serum bilirubin = 1.5 x ULN Absolute neutrophil count (ANC) =
1,500/uL Platelets = 100,000/uL Hemoglobin = 8.0 g/dL Serum creatinine OR Measured or
calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl)
Serum creatinine =1.5 X upper limit of normal (ULN) OR =60 mL/min for subject with
creatinine levels > 1.5 X institutional ULN
- Creatinine clearance should be calculated per institutional standard.
- Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of
birth control or be surgically sterile, or abstain from heterosexual activity for
the course of the study through 120 days after the last dose of study medication
(Reference Section 8.7.2). Subjects of childbearing potential are those who have
not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of
study therapy.
- provision of a signed written informed consent
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
- Active or history of autoimmune disease or immune deficiency, including MG, myositis,
hepatitis, SLE, RA, IBD or GBS)
- Severe co-morbid illness and/or active infections
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has a known history of active TB (Bacillus Tuberculosis)
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer
- Pregnant or lactating women
- History of documented congestive heart failure; angina pectoris requiring medication;
evidence of tranasmural myocardial infarction on ECG; poorly controlled hypertension;
clinically significant valvular heart disease; or high risk of uncontrollable
arrhythmia
- Active CNS metastases not controllable with radiotherapy or corticosteroids (however,
CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma
knife surgery or surgery or radiotherapy or steroid)
- Must not have undergone a major surgical procedure < 4 weeks or radiotherapy <2 weeks
prior to D1 of treatment
- Administration of a live, attenuated vaccine within 4 weeks before study treatment
- Treatment with systemic immunosuppressive medication (including prednisone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor
agents) within 2 weeks prior to D1 of treatment
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