Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

OBJECTIVES:

Primary

- To determine the response rate of metastatic uveal melanoma when treated with
cixutumumab (IMC-A12).

- To determine the safety and tolerability of IMC-A12 in patients with metastatic uveal
melanoma.

Secondary

- To determine the disease control rate in patients treated with IMC-A12.

- To determine the duration of response in patients treated with IMC-A12.

- To determine the progression-free survival and overall survival of patients treated
with IMC-A12.

- To correlate the presence of GNAQ and GNA11 mutations with response to IMC-A12.
(Exploratory)

- To correlate the expression of IGF-1R with response to IMC-A12. (Exploratory)

- To determine the effect of IMC-A12 on expression of proteins involved in initiation,
growth, and spread of uveal melanoma cells. (Exploratory)

- To determine resistance mechanisms to IMC-A12. (Exploratory)

OUTLINE: This is a multicenter study.

Patients receive cixutumumab IV over 1 hour on days 1 and 15. Courses repeat every 4 weeks
in the absence of disease progression or unacceptable toxicity.

Archived and fresh tumor tissue and serum samples may be collected for correlative studies.

After completion of study treatment, patients are followed up for 30 days and then every 3
months for 1 year.

DISEASE CHARACTERISTICS:

- Patients must have a history of uveal melanoma and documented metastatic disease
(CTEP Simplified Disease Classification 10053571)

- Patients must have at least one unidimensional measurable lesion

- A cutaneous lesion must be ≥ 10 mm by caliper measure

- A visceral or nodal or soft tissue lesion must be clearly measurable > 20 mm
with conventional techniques or > 10 mm with spiral CT scan

- Bone lesions are not considered measurable

- No patients whose site of primary melanoma is not uveal

- Patients must have 15-20 slides of metastatic tissue for enrollment; this may take
the form of archived tissue or fresh tissue biopsy

- Patients with one or more of the following as the only manifestations of disease are
ineligible

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusions

- Carcinomatous lymphangitis

- No patients with symptomatic central nervous system (CNS) metastasis, including those
with CNS metastasis who require oral steroids

PATIENT CHARACTERISTICS:

- 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

- Platelet count ≥ 100,000/mm³

- AST(SGOT)/ALT(SGPT) ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver
metastases present)

- Total bilirubin < 1.5 times ULN

- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Fasting serum glucose < 120 mg/dL OR < institutional ULN

- Patients must have no angina at rest

- No patients who are pregnant or nursing

- 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 up to 3 months after the last dose of
cixutumumab (IMC-A12)

- Patients must have the ability to understand and the willingness to sign a written
informed consent

- No patients who have a current history of neoplasm other than the entry diagnosis
except for curatively treated non-melanoma skin cancer, carcinoma in situ of the
prostate or cervix, or other cancers treated for cure and with a disease-free
survival longer than 2 years

- No patients with current active infections requiring anti-infectious treatment (e.g.,
antibiotics, antivirals, or antifungals)

- No 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

- No patients with Gilbert syndrome

- No HIV-positive patients with an absolute CD4 count < 300 K/uL

- No patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to IMC-A12

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- One prior systemic chemotherapy and any number of immunotherapies or vaccine
therapies are allowed

- At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic,
vaccine or other therapy unless patients have progressed during therapy (at
least 4 weeks since prior adjuvant chemotherapy)

- If progression occurred during therapy, patient must have recovered from
any side effects

- Patients are not required to have had prior therapy

- 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 3,000 cGy to
fields including substantial marrow

- At least 4 weeks (28 days) since prior radiotherapy

- 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 not been radiated

- Patients may not be receiving any other investigational agents

- No patients with a history of treatment with other agents targeting the insulin-like
growth factor pathway