IMC-A12 in Treating Patients With Advanced Liver Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma
• Intervention / Treatment: Biological: cixutumumab; Procedure: computed tomography; Procedure: contrast-enhanced magnetic resonance imaging

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (monoclonal antibody therapy); 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; Given IV; Other Names: anti-IGF-1R recombinant monoclonal antibody IMC-A12; IMC-A12; Procedure: computed tomography; Undergo contrast-enhanced computed tomography; Other Names: tomography, computed; Procedure: contrast-enhanced magnetic resonance imaging; Undergo contrast-enhanced magnetic resonance imaging; Other Names: Contrast-enhanced MRI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ghassan Abou-Alfa, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: March 19, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: NCI-2009-00283 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA008748 (U.S. NIH Grant/Contract); MSKCC-08015; CDR0000589633; 08-015 (Memorial Sloan-Kettering Cancer Center); 8124 (Other Identifier: CTEP); N01CM62206 (U.S. NIH Grant/Contract)