IMC-A12 in Treating Patients With Advanced Liver Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00639509
First received: March 19, 2008
Last updated: May 7, 2014
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Biological: cixutumumab
Procedure: computed tomography
Procedure: contrast-enhanced magnetic resonance imaging
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PFS Rate [ Time Frame: At 4 months ] [ Designated as safety issue: No ]
    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.

  • Best Overall Response Rate (ORR) [ Time Frame: From the start of the treatment until disease progression/recurrence ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Median Overall Survival [ Time Frame: Post-Treatment ] [ Designated as safety issue: No ]
    Median Overall Survival


Enrollment: 24
Study Start Date: March 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: tomography, computed
Procedure: contrast-enhanced magnetic resonance imaging
Undergo contrast-enhanced magnetic resonance imaging
Other Name: Contrast-enhanced MRI

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639509

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Ghassan Abou-Alfa Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00639509     History of Changes
Other Study ID Numbers: NCI-2009-00283, NCI-2009-00283, MSKCC-08015, CDR0000589633, 08-015, 8124, P30CA008748, N01CM62206
Study First Received: March 19, 2008
Results First Received: September 25, 2013
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014