Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye
Condition: Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma
MeSH terms: Melanoma; Uveal Neoplasms
Intervention: Cixutumumab; Laboratory biomarker analysis
Intervention description: 10 mg/kg IV infusion over 1 hour every 2 weeks with treatment cycle defined as 4 weeks; Correlative studies
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 17 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving cixutumumab works in treating patients with
      metastatic melanoma of the eye. Monoclonal antibodies, such as cixutumumab, can block tumor
      growth in different ways. Some block the ability of tumor cells to grow and spread. Others
      find tumor cells and help kill them or carry tumor-killing substances to them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a history of uveal melanoma and documented metastatic disease

          -  Patients must have at least one unidimensionally measurable lesion; if this is a
             cutaneous lesion it must be at least 10 mm by caliper measure; if it is a visceral or
             nodal or soft tissue lesion, it must be clearly measurable > 20 mm with conventional
             techniques or > 10 mm with spiral CT scan; bone lesions are not considered measurable

          -  One prior systemic chemotherapy and any number of immunotherapies or vaccine therapies
             are allowed; prior treatment with hepatic arterial chemotherapy infusion or perfusion
             or chemoembolization of liver metastasis is allowed; prior treatment with radiation
             therapy is allowed but not more than 3000 cGy to fields including substantial marrow;
             patients are not required to have had prior therapy

               -  At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic,
                  vaccine or other therapy unless patients have progressed during therapy; if
                  progression occurred during therapy, patient must have recovered from any side
                  effects

               -  At least 4 weeks (28 days) since prior radiotherapy and prior adjuvant
                  chemotherapy

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 -
             2

          -  Patients must have a life expectancy of at least 3 months

          -  Leukocytes > 3,000/mm3

          -  Absolute neutrophil count ≥ 1,500/mm3

          -  Hemoglobin ≥ 9.0 g/dL

          -  Platelets ≥ 100,000/mm3

          -  Aspartate transaminase-alanine transaminase ratio (AST(SGOT)/ALT(SGPT)) ≤ 3 times
             institutional upper limit of normal (ULN); ≤ 5 times institutional ULN if liver
             metastases present

          -  Total bilirubin < 1.5 times institutional ULN

          -  Creatinine < 1.5 times institutional ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2
             for patients with creatinine levels above institutional normal

          -  Fasting serum glucose < 120 mg/dL or < institutional ULN

          -  Patients must have no angina at rest

          -  The effects of IMC-A12 on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason and because monoclonal antibodies could be
             teratogenic, women of child-bearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation and for 3 months after the last dose
             of IMC-A12; should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately

          -  Both men and women and members of all races and ethnic groups are eligible for this
             trial

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent form indicating that they are aware of the investigational nature of
             this study and in keeping with the policies of the institution

        Exclusion Criteria:

          -  Patients whose site of primary melanoma is not uveal

          -  Patients who have a current history of neoplasm other than the entry diagnosis except
             for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or
             other cancers treated for cure and with a disease-free survival longer than 5 years

          -  Patients with symptomatic central nervous system metastasis including those with
             central nervous system (CNS) metastasis who require oral steroids for cerebral edema
             or have progression on CT/MRI

          -  Patients who are pregnant or nursing and patients who are not practicing an acceptable
             method of birth control; patients may not breast-feed while on this study; pregnant
             women are excluded from this study because IMC-A12 is a monoclonal antibody with the
             potential for teratogenic or abortifacient effects; because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with IMC-A12, breastfeeding women are excluded

          -  Patients with current active infections requiring anti-infectious treatment (e.g.,
             antibiotics, antivirals, or antifungals)

          -  Patients with poorly controlled diabetes mellitus; patients with a history of diabetes
             mellitus are allowed to participate, provided that their blood glucose is within
             normal range (fasting < 120 mg/dL or below institutional ULN) and that they are on a
             stable dietary or therapeutic regimen for this condition

          -  Patients with unstable or serious concurrent medical conditions are excluded; examples
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
             months) myocardial infarction, uncontrolled major seizure disorder, spinal cord
             compression, superior vena cava syndrome, or any psychiatric disorder that prohibits
             obtaining informed consent

          -  Patients with one or more of the following as the only manifestations of disease are
             ineligible: leptomeningeal disease, ascites, pleural/pericardial effusions,
             carcinomatous lymphangitis

          -  Patients with Gilbert's Syndrome

          -  Patients must not have had major surgery within the past 14 days

          -  Patients must not receive any concurrent chemotherapy or immunotherapy while on study;
             only palliative radiotherapy is permitted to symptomatic lesions in which event the
             irradiated lesions may not be considered target or non-target lesions for response;
             palliative radiation immediately before or during the study is acceptable provided
             there is evaluable disease that has been radiated; palliative radiation is acceptable
             provided that the irradiated lesions are not used to determine response assessment

          -  HIV-positive patients with an absolute CD4 count < 300 K/uL

          -  Patients may not be receiving any other investigational agents

          -  Patients with a history of treatment with other agents targeting the insulin-like
             growth factor pathway

          -  Patients with a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to IMC-A12