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A Study of IMC-A12 in Combination With Sorafenib in Patients With Advanced Cancer of the Liver
This study is currently recruiting participants.
Verified October 2011 by ImClone LLC

First Received on May 20, 2009.   Last Updated on October 14, 2011   History of Changes
Sponsor: ImClone LLC
Information provided by (Responsible Party): ImClone LLC
ClinicalTrials.gov Identifier: NCT00906373
  Purpose

To determine if IMC-A12 given in combination with Sorafenib is safe and effective for patients with advanced liver cancer.


Condition Intervention Phase
Hepatocellular Carcinoma
 Biological: IMC-A12 (cixutumumab)
Drug: sorafenib
 Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Phase 2 Study Evaluating IMC-A12 in Combination With Sorafenib as First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer
Drug Information available for: Sorafenib Sorafenib tosylate
U.S. FDA Resources

Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Maximum concentration (Cmax) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Maximum concentration (Cmax) Cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Minimum concentration (Cmin) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Minimum concentration (Cmin) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Minimum concentration (Cmin) Cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Half-Life (t 1/2) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Half-Life (t 1/2) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Half-Life (t 1/2) cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Clearance (CL) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Clearance (CL) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Clearance (CL) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Clearance (CL) cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Area Under the Curve (AUC) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Area Under the Curve (AUC) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Area Under the Curve (AUC) cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Volume of Distribution at Steady State (Vd) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Within 14 days prior to the first infusion, immediately after the 1-hour infusion, 2-hours after the start of the infusion.

  • Volume of Distribution at Steady State (Vd) cycle 1 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion

  • Volume of Distribution at Steady State (Vd) cycle 1 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion

  • Volume of Distribution at Steady State (Vd) cycle 1 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 2 infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Immediately prior to the third infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Maximum concentration (Cmax) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to Cycle 4.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Immediately prior to the third infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Minimum concentration (Cmin) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to Cycle 4.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Immediately prior to the third infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Half-Life (t 1/2) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to Cycle 4.

  • Clearance (CL) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Immediately prior to the third infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Clearance (CL) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to Cycle 4.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Imediately prior to the third infusion, 2 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Area Under the Curve (AUC) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 4 infusion..

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    Imediately prior to the third infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 44 ] [ Designated as safety issue: No ]
    24 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 45 ] [ Designated as safety issue: No ]
    48 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 46 ] [ Designated as safety issue: No ]
    72 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    168 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 53 ] [ Designated as safety issue: No ]
    240 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    336 hours after the start of the infusion.

  • Volume of distribution at steady state (Vd) cycle 3 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    504 hours after the start of the infusion, immediately prior to the Cycle 4 infusion..

  • Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Serum Anti-cixutumumab Antibody Assessment (immunogenicity) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: May 2009
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort 1
Treatment cycles will repeat until there is evidence of progressive disease (PD), toxicity, or Withdrawal. If any participant experiences a dose-limiting toxicity (DLT), an additional 3 patients will be enrolled at this dose level (for a total of 6). If no further DLTs, enrollment into Cohort 2 will occur.
 Biological: IMC-A12 (cixutumumab)
intravenous infusions 10 mg/kg on day 1 of each 3 week cycle
Other Name: cixutumumab
Drug: sorafenib
400 mg twice per day orally
Other Name: Nexavar
Active Comparator: Cohort 2
Treatment cycles will repeat until there is evidence of progressive disease (PD), toxicity, or Withdrawal.
 Biological: IMC-A12 (cixutumumab)
intravenous infusions 20 mg/kg on day 1 of each 3 week cycle
Other Name: cixutumumab
Drug: sorafenib
400 mg twice per day orally
Other Name: Nexavar

Detailed Description:

The purpose of this study is to determine progression free survival (PFS) in patients with unresectable hepatocellular carcinoma who have received no prior systemic therapy when treated with IMC-A12 administered every three weeks in combination with oral sorafenib administered twice daily.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has histologically or cytologically confirmed, unresectable HCC
  • The patient has at least one target lesion measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Target lesion(s) must not lay within a previously irradiated, ablated, or chemoembolized area. If a lesion does lie in such an area, there must be evidence of growth on successive imaging studies, including tumor hypervascularity, in order for such a lesion to be considered a target lesion
  • The patient has not received prior systemic therapy for HCC. Patients may have received prior embolization, chemoembolization, intra-arterial chemotherapy infusion, ethanol injection, radiofrequency ablation, or cryosurgery
  • The patient has fasting serum glucose < 160 mg/dL or below the ULN and/or hemoglobin A1C < 7%. If baseline nonfasting glucose < 160 mg/dL, fasting glucose measurement is not required
  • The patient has the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • The patient has brain metastases
  • The patient has acute hepatitis
  • The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range and that they are on a stable dietary or therapeutic regimen for this condition
  • The patient has congestive heart failure > class II NYHA, unstable angina pectoris, new onset of angina pectoris, myocardial infarction within the past 6 months, or cardiac ventricular arrhythmias requiring antiarrhythmic therapy
  • The patient has experienced a hemorrhage or bleeding event ≥ NCI-CTCAE Grade 3 within 4 weeks prior first dose of study therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906373

Contacts
Contact: There may be multiple sites in this clinical trial, inquire by e-mail. ClinicalTrials@imclone.com

Locations
United States, Arizona
ImClone Investigational Site Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
ImClone Investigational Site Recruiting
Los Angeles, California, United States, 90095
United States, Illinois
ImClone Investigational Site Recruiting
Chicago, Illinois, United States, 60611
United States, Louisiana
ImClone Investigational Site Recruiting
Metairie, Louisiana, United States, 70006
United States, Massachusetts
ImClone Investigational Site Recruiting
Burlington, Massachusetts, United States, 01805
United States, New York
ImClone Investigational Site Recruiting
New York, New York, United States, 10033
United States, Pennsylvania
ImClone Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
ImClone LLC
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT00906373     History of Changes
Other Study ID Numbers: 13931, CP13-0812, I5A-IE-JAEG
Study First Received: May 20, 2009
Last Updated: October 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Hepatocellular Carcinoma
Liver Neoplasms
Antibodies, Monoclonal

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
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012



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