IMC-A12 in Treating Patients With Advanced Liver Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

Treatments: Procedure: computed tomography; Biological: cixutumumab; Procedure: contrast-enhanced magnetic resonance imaging

Study type: Interventional

Funder types: NIH

Identifiers

NCT00639509

MSKCC-08015

N01CM62206 (U.S. NIH Grant/Contract)

P30CA008748 (U.S. NIH Grant/Contract)

CDR0000589633

NCI-2009-00283 (Registry Identifier)

08-015 (Other Identifier)

8124 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Treatment (monoclonal antibody therapy)

Experimental group

Description:

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.

Treatment:

Procedure: contrast-enhanced magnetic resonance imaging

Biological: cixutumumab

Procedure: computed tomography