IMC-A12 in Treating Patients With Advanced Liver Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma

Conditions
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Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

Intervention / Treatment
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* Biological: cixutumumab
* Procedure: computed tomography
* Procedure: contrast-enhanced magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (monoclonal antibody therapy)<br>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. | Biological: cixutumumab<br>* Given IV<br>* Other names: IMC-A12;Procedure: computed tomography<br>* Undergo contrast-enhanced computed tomography<br>* Other names: tomography, computed;Procedure: contrast-enhanced magnetic resonance imaging<br>* Undergo contrast-enhanced magnetic resonance imaging<br>* Other names: Contrast-enhanced MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Rate | PFS defined as the time from first date of first treatment on the study until such time as progressive disease is confirmed or upon patient death if disease progression has not been evident at that time. A Simon's optimal two stage design will be used with the following assumption: a 4 months PFS of 62% is considered acceptable while a 4 months PFS of 42% is not acceptable. | At 4 months | 
| Best Overall Response Rate (ORR) | Best overall ORR will be defined as the proportion of patients achieving either confirmed partial response (PR) or confirmed complete response (CR). A Simon's optimal two stage design will be used with the following assumption: ORR of more than 20% is acceptable and an ORR less than 5% is not acceptable. | From the start of the treatment until disease progression/recurrence | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | Median Overall Survival | Post-Treatment |