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IMC-A12 in Treating Patients With Advanced Liver Cancer
This study has been suspended.
First Received: March 19, 2008   Last Updated: July 11, 2009   History of Changes
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00639509
  Purpose

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well IMC-A12 works in treating patients with advanced liver cancer.


Condition Intervention Phase
Liver Cancer
Biological: cixutumumab
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
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:
  • Progression-free survival (PFS) rate at 4 months [ Designated as safety issue: No ]
  • Best overall response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall and median survival [ Designated as safety issue: No ]
  • Safety, tolerability, and adverse events profile [ Designated as safety issue: Yes ]
  • Differences in the PFS of patients who are hepatitis B positive/hepatitis C negative versus patients who are hepatitis B negative/hepatitis C positive [ Designated as safety issue: No ]
  • Ability of the volumetric method to assess response to treatment compared to standard RECIST criteria [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: March 2008
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • To determine the median overall survival of patients treated with this drug.
  • To evaluate the safety, tolerability, and adverse events profile of this drug in these patients.
  • 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.
  • To store pre-therapy paraffin embedded tumor tissue for future tissue-based correlative studies.
  • To evaluate tumor necrotic areas using a new volumetric method of assessing non-viable tumor as a correlate for response.
  • 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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 CONCURRENT THERAPY:

  • 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
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
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Ghassan Abou-Alfa, MD Memorial Sloan-Kettering Cancer Center
Investigator: Leonard B. Saltz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center ( David Paul Kelsen )
Study ID Numbers: CDR0000589633, MSKCC-08015
Study First Received: March 19, 2008
Last Updated: July 11, 2009
ClinicalTrials.gov Identifier: NCT00639509     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
adult primary hepatocellular carcinoma

Study placed in the following topic categories:
Liver Neoplasms
Liver Diseases
Digestive System Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Gastrointestinal Neoplasms
Hepatocellular Carcinoma
Adenocarcinoma
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Liver Neoplasms
Liver Diseases
Neoplasms
Digestive System Diseases
Neoplasms by Site
Digestive System Neoplasms
Neoplasms by Histologic Type
Carcinoma, Hepatocellular
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

ClinicalTrials.gov processed this record on September 10, 2009