Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

Inclusion Criteria

• •Histologic diagnosis of unresectable or advanced mucosal melanoma arising from the head/neck (e.g. sinonasal, oral cavity, conjunctival), gastrointestinal (e.g. anorectal, esophageal), or genitourinary (e.g. vulvovaginal, urethral) sites.
• •Measurable disease
• •1. Initial study entry: Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1).
• •2. Triplet arms: assessable disease required. RECIST 1.1 measurable disease is not required.
• •Prior therapy
• •1. Initial study entry: No prior systemic therapy (adjuvant or metastatic).
• •2. Triplet arms: Only prior systemic therapy is nivolumab + axitinib on this trial.
• •ECOG performance status of 0-2.
• •Asymptomatic untreated brain metastases are allowed. Symptomatic brain metastases that have undergone local therapy with RT or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed.
• •Screening laboratory parameters:
• •1. White blood cell (WBC) count ≥ 2000/μL;
• •2. Absolute neutrophil count (ANC) ≥ 1500/μL;
• •3. Platelets ≥ 100,000/μL;
• •4. Hemoglobin (Hgb) ≥ 9 g/dL;
• •5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN);
• •6. Total bilirubin ≤ 1.5 × ULN (\< 3 mg/dL for subjects with Gilbert's disease);
• •7. Estimated glomerular filtration rate (GFR) ≥ 30 mL/min;either Cockcroft Gault or a cancer-specific GFR Model such as the camGFR version 2 can be used;
• •Age ≥ 18 years.
• •Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. \[Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).\] Nonsterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception from Day 1 and for 31 weeks after receipt of the final dose of investigational product.
• •Acceptable methods of effective contraception are described in the following:
• •Barrier Methods (Male condom plus spermicide, cap plus spermicide, or diaphragm plus spermicide).
• •Intrauterine Device Methods (Copper T, or Levonorgestrelreleasing intrauterine system (e.g., Mirena®), also considered a hormonal method).
• •Hormonal Methods (Implants, hormone shot or injection, combined pill, mini pill, or Patch).