Phase II Study of IMC-A12 in Patients With Mesothelioma Who Have Been Previously Treated With Chemotherapy

-INCLUSION CRITERIA:

• Subjects must have histologically confirmed pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection. The diagnosis will be confirmed by the pathology department / Center for Cancer Research (CCR) / National Cancer Institute (NCI).
• Patients must have had at least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan.
• Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study and must have evidence of stable or progressive disease to be eligible.
• Age greater than or equal to 18 years. Since mesothelioma is extremely rare in children they are excluded from this study.
• Life expectancy of greater than 3 months.
• Performance status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
• Patients must have adequate organ and marrow function (as defined below).
• leukocytes greater than or equal to 3,000/mm^3
• absolute neutrophil count greater than or equal to 1,500/mm^3
• hemoglobin greater than or equal to 9 g/dL
• platelets greater than or equal to 100,000/ mm^3
• total bilirubin less than or equal to 1.5 times institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 3 times institutional ULN

(5 times if liver function test (LFT) elevations due to liver metastases)

• creatinine less than or equal to 1.5 times institutional ULN

OR

• creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine

levels above institutional normal

Patients may be transfused to obtain a hemoglobin of greater than or equal to 9 g/Dl.

• The patient must have fasting serum glucose 50 copies HIV/ml), and/or acquired immune deficiency syndrome (AIDS)-defining illnesses will be excluded due to the possibility that IMC-A12 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to IMC-A12. HIV positive patients with mesothelioma not meeting the above criteria can be considered for inclusion in the study.
• Patients may not be receiving any other investigational agents.
• History of another invasive malignancy in the last five years. Adequately treated non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed.
• Prior treatment with drugs of the IGF-1R inhibitor class.
• Patients with tumor amenable to potentially curative therapy as assessed by the investigator. In patients with peritoneal mesothelioma who have had no prior surgery, a surgical consultation will be obtained to see if the patient is a candidate for debulking surgery.
• Pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody to IGF-1R with the potential for teratogenic or abortifacient effects. Immunoglobulin G (IgG) antibody may also potentially be secreted in milk and therefore breastfeeding women should be excluded. Because of the potential of teratogenic or abortifacient effects women of childbearing potential and men must agree to use adequate contraception (barrier methods) before, during the study and for a period of 3 months after the last dose of the investigational agent.
• Patients must not be on hormonal forms of birth control or hormone replacement therapy, as this may affect the study drug. Patients must be off hormonal forms of birth control or hormone replacem