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

Phase 2
18 Years
Not Enrolling
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

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Trial Information

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


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

II. To determine the best overall response rate in patients treated with this drug.


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

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

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

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

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PFS rate

Outcome Description:

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.

Outcome Time Frame:

At 4 months

Safety Issue:


Principal Investigator

Ghassan Abou-Alfa

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

Related Keywords:

  • Adult Primary Hepatocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Memorial Sloan Kettering Cancer Center New York, New York  10021