imc-a12 in treating patients with advanced liver cancer

Conditions: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

Summary: this phase ii trial is studying how well imc-a12 works in treating patients with advanced liver cancer. monoclonal antibodies, such as imc-a12, 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.

primary objectives: i. to determine the progression-free survival (pfs) at 4 months in patients with advanced hepatocellular carcinoma (hcc) treated with anti-igf-1r recombinant monoclonal antibody imc-a12. ii. to determine the best overall response rate in patients treated with this drug. secondary objectives: i. to determine the median overall survival of patients treated with this drug. ii. to evaluate the safety, tolerability, and adverse events profile of this drug in these patients. iii. to perform a subgroup analysis to compare pfs of patients with advanced hcc who are hepatitis b positive/hepatitis c negative versus patients who are hepatitis b negative/hepatitis c positive treated with this drug. iv. to store pre-therapy paraffin embedded tumor tissue for future tissue-based correlative studies. v. to evaluate tumor necrotic areas using a new volumetric method of assessing non-viable tumor as a correlate for response. vi. to prospectively validate and compare the clip and the gdetch staging systems and additional prognostic factors. outline: patients receive anti-igf-1r recombinant monoclonal antibody imc-a12 iv over 1 hour once weekly. treatment continues in the absence of disease progression or unacceptable toxicity. patients undergo serum sample collection at baseline for future tissue-based correlative studies. previously collected paraffin embedded tumor tissue samples are also stored for future correlative studies. after completion of study treatment, patients are followed every 3 months for at least 1 year.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed hepatocellular carcinoma * unresectable, locally advanced, or metastatic disease * measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral ct scan * child's pugh score a5, a6, b7, or b8 * no known brain metastases * no history of primary cns tumors * ecog performance status (ps) 0-2 or karnofsky ps 60-100% * life expectancy \> 3 months * leukocytes ≥ 3,000/mcl * absolute neutrophil count ≥ 1,500/mcl * platelet count ≥ 75,000/mcl * total bilirubin ≤ 2 times upper limit of normal (uln) * ast/alt ≤ 2.5 times uln * pt/inr ≤ 1.7 times uln * creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 ml/min * fasting serum glucose ≤ 125 mg/dl * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no clinical encephalopathy * no history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-igf-1r recombinant monoclonal antibody imc-a12 * no poorly controlled diabetes mellitus * patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range (fasting blood glucose \< 120 mg/dl or below uln) and patient is on a stable dietary or therapeutic regimen for this condition * no concurrent uncontrolled illness including, but not limited to, any of the following: * ongoing or active infection * symptomatic congestive heart failure * unstable angina pectoris * cardiac arrhythmia * psychiatric illness or social situation that would preclude compliance with study requirements * no history of seizures not well controlled with standard medical therapy * no history of stroke * no history of another primary cancer except for the following: * curatively resected nonmelanoma skin cancer * curatively treated carcinoma in situ of the cervix * other primary solid tumor with no known active disease present that in the opinion of the investigator would not affect treatment outcome * prior local therapy (i.e., surgery, radiotherapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) allowed provided the target lesion has not been treated with local therapy and/or the target lesion within the field of local therapy has shown an increase of ≥ 25% in size * at least 4 weeks since prior local therapy * no prior systemic therapy except for sorafenib tosylate * no prior agents targeting the igf or igf-1r pathway * no concurrent combination antiretroviral therapy for hiv-positive patients * no other concurrent investigational agents * no concurrent anticancer therapy