Pharmacokinetic Study of Liposomal Vincristine in Patients With Malignant Melanoma & Hepatic Dysfunction
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: Vincristine Sulfate Liposomes Injection
Intervention description: Marqibo (VSLI) 1.0 mg/m2 delivered by intravenous infusion over 1 hour every 2 weeks.
Intervention MeSH terms: Vincristine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to see how vincristine, when placed in an oil droplet called a
      liposome (VSLI), is absorbed, distributed (moved around) and excreted from the the body
      (pharmacokinetics). This study will also assess the safety of VSLI and to see if VSLI will
      slow the growth or shrink tumors in patients with metastatic melanoma that has resulted in
      liver impairment, and who have relapsed after previous therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed, surgically nonresectable Stage III or IV
             metastatic cutaneous, mucosal, or choroidal melanoma, and not be eligible for a
             treatment protocol of a higher priority.

          -  Patients must have secondary tumor involvement of the liver confirmed by CT scan and a
             bilirubin level of 1.6-3.0 mg/dL (National Cancer Institute, Common Terminology
             Criteria for Adverse Events Grade 2) (MD Anderson Cancer Center normal range is 0-1.0
             mg/dL).

          -  Patients must have bidimensionally measurable disease.

          -  Patients with nonchoroidal melanoma must have received prior chemotherapy for
             metastatic disease with cytotoxic or biological drugs. Patients with choroidal
             melanoma may or may not have received prior chemotherapy for metastatic disease with
             cytotoxic or biological drugs.

          -  Patients must have a Performance Status of 0, 1, 2, or 3 (Zubrod Scale).

          -  Patients must have recovered from the adverse effects of prior chemotherapy (including
             cytotoxic agents and biological response modifiers), and/or irradiation therapy.

          -  Patients must have an absolute neutrophil count ≥1.0 x 10*9/L and a platelet count of
             ≥100 x 10*9/L.

          -  Patients must have adequate renal function demonstrated by a creatinine level of ≤2.0
             mg/dL.

          -  Patients must have a life expectancy of >8 weeks.

          -  Patients must provide a signed informed consent document indicating that they are
             aware of the investigational nature of this study in keeping with the policies of the
             hospital.

        Exclusion Criteria:

          -  Patients treated with radiotherapy, chemotherapy, immunotherapy, vaccine treatment
             and/or alternative anticancer treatments (including investigational drugs) within 3
             weeks prior to study enrollment.

          -  Patients treated with hepatic chemo-embolization within 4 weeks prior to study
             enrollment.

          -  Patients with severe hepatic impairment demonstrated by plasma ammonia levels >105
             mMol/L or serum albumin <2.0 g/dL or serum bilirubin >3.0 mg/dL.

          -  Patients with serious intercurrent illness.

          -  Patients who have had major surgery within 4 weeks of enrollment.

          -  Patients with advanced symptomatic central nervous system (CNS) involvement by
             melanoma and those on phenytoin or requiring steroids for brain metastases, spinal
             cord compression, or meningeal "carcinomatosis".Patients with asymptomatic and stable
             metastatic CNS disease can be enrolled.

          -  Patients receiving treatment with phenytoin and/or corticosteroids within 1 week of
             enrollment. Patients must remain off of these medications for the duration of the
             treatment phase of the study.

          -  Patients with a history of neurological disorders unrelated to chemotherapy (including
             familial neurological diseases and acquired demyelinating disorders).

          -  Patients with Grade 3 or greater sensory, motor or autonomic neuropathy at screening
             from any cause.

          -  Patients receiving treatment with drugs known to inhibit or induce hepatic drug
             metabolism by cytochrome P450-3A4 isoenzymes and/or P-glycoprotein within 1 week of
             study enrollment. Patients must remain off of these drugs until the collection of the
             Cycle 4 pretreatment PK sample.

          -  Patients with past or current history of liver parenchymal or hepatobiliary disease
             unrelated to cancer (including but not limited to conditions such as liver cirrhosis,
             acute/chronic hepatitis, ascending cholangitis, etc).

          -  Patients who are pregnant or lactating. Females of childbearing potential must have a
             negative urine or blood pregnancy test at screening. Both men and women must be
             practicing an adequate method of birth control for the duration of the study.
             Acceptable methods of birth control include use of an intrauterine device (IUD), oral
             contraceptive pills, implanted, transdermal, or injected contraceptives, barrier
             methods with spermicide, and abstinence.

          -  Patients who are unable to return for follow up re-evaluation and assessment of
             response to VSLI.