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A Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver

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ClinicalTrials.gov Identifier: NCT00906373
Recruitment Status : Completed
First Posted : May 21, 2009
Results First Posted : June 4, 2018
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg) Biological: IMC-A12 (cixutumumab) - 20 mg/kg Drug: Sorafenib Phase 2

Detailed Description:
The purpose of this study is to determine progression-free survival (PFS) in participants 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : May 2009
Actual Primary Completion Date : October 2012
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Active Comparator: Cohort 1, IMC A12 - 10 mg/kg
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 participants 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) - 10 milligrams/kilogram (mg/kg)
intravenous infusions 10 mg/kg on Day 1 of each 3-week cycle
Other Names:
  • cixutumumab
  • LY3012217

Drug: Sorafenib
400 milligrams (mg) twice per day orally

Active Comparator: Cohort 2, IMC A12 20 - mg/kg
Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.
Biological: IMC-A12 (cixutumumab) - 20 mg/kg
intravenous infusions 20 mg/kg on Day 1 of each 3-week cycle
Other Names:
  • cixutumumab
  • LY3012217

Drug: Sorafenib
400 milligrams (mg) twice per day orally




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Date of first dose of study drug up PD or death up to 12 months ]
    PFS is defined as the time from date of first dose of study drug until the date of objective PD or death due to any cause, whichever occurs first. PD defined as a ≥20% increase in the sum of the longest diameter (LD) of target lesions using as reference the smallest sum LD since baseline or ≥1 new lesions. Participants who died without PD were considered to have progressed on the date of death. Participants who were alive and without PD were censored at the time of the last objective tumor assessment. Participants who did not progress and are subsequently lost to follow-up were censored at the date of their last objective tumor assessment before loss to follow-up. Participants who progressed or died after ≥2 missed tumor assessment visits were censored at the date of their last objective tumor assessment before missed assessments. Participants who begin a new anticancer therapy were censored at the date of their last objective tumor assessment before initiation of new therapy.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs) [ Time Frame: First day of treatment up to 22 months ]
    Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.

  2. Pharmacokinetic (PK): Maximum Concentration (Cmax) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 hour (h), 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  3. PK: Minimum Concentration (Cmin) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  4. PK: Half-Life (t1/2) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  5. PK: Clearance (CL) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  6. PK: Area Under the Concentration Versus Time Curve (AUC) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  7. PK: Volume of Distribution at Steady State (Vss) Cycle 1 [ Time Frame: Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2) ]
  8. PK: Cmax Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  9. PK: Cmin Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  10. PK: t1/2 Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  11. PK: CL Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  12. PK: AUC Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  13. PK: Vss Cycle 3 [ Time Frame: Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4) ]
  14. Percentage of Participants With Complete Response (CR) and Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Date of first dose of study drug to PD up to 12 months ]
    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR was defined as the disappearance of all target and nontarget lesions and the normalization of tumor marker levels. PR was defined as having a ≥30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Participants who did not have a tumor response assessment for any reason were considered nonresponders and were included in the denominator when calculating the response rate. Percentage of participants was calculated as: CR + PR / total number of participants in the treatment group * 100.

  15. Overall Survival (OS) [ Time Frame: Date of first dose of study drug to date of death up to 22 months ]
    OS was defined as the time from the date of first dose of study drug to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.

  16. Time to Disease Progression (TTP) [ Time Frame: Date of first dose of study drug to date of PD up to 12 months ]
    TTP is defined as the time from the date of first dose of study drug until the date of objective disease progression. Participants without PD were censored at the time of the last objective tumor assessment. Participants who did not progress and lost to follow-up were censored at the date of the last objective tumor assessment before loss to follow-up. Participants who began new anticancer therapy prior to PD or death were censored at date of last tumor assessment prior to new therapy. Participants who died or had PD after ≥2 missed tumor assessments were censored at date of last tumor assessment prior to the missed assessments.

  17. Duration of Response (DOR) [ Time Frame: Date of first occurrence of CR or PR to first date of PD or death up to 8 months ]
    Duration of CR or PR was defined as time from first objective assessment of CR or PR until first date of PD or death from any cause. Response was defined using RECIST v 1.0 criteria. CR was defined as disappearance of all target and nontarget lesions and normalization of tumor marker levels. PR was defined as a ≥30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. PD defined as a ≥20% increase in the sum of LD of target lesions using as reference the smallest sum LD since baseline or ≥1 new lesions. Participants with no PD, who discontinued treatment for toxicity or a reason other than PD, or were lost to follow-up, were censored at date of last tumor assessment. Participants who began new anticancer therapy prior to PD or death were censored at date of last tumor assessment prior to new therapy. Participants who died or had PD after ≥2 missed tumor assessments were censored at date of last tumor assessment prior to the missed assessments

  18. The Number of Participants With Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity) [ Time Frame: Predose, immediately prior to the first Cycle 3 and Cycle 5 infusions (3-week cycle) and 30 days after last dose of study drug ]
    A participant's serum sample was considered positive for antibodies against cixutumumab if it exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-cixutumumab level seen in healthy untreated individuals. A participant was considered to have an anti-cixutumumab response if there were 2 consecutive positive samples or if the final sample tested was positive.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The participant has histologically or cytologically confirmed, unresectable HCC
  • The participant 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 participant has not received prior systemic therapy for HCC. Participants may have received prior embolization, chemoembolization, intra-arterial chemotherapy infusion, ethanol injection, radiofrequency ablation, or cryosurgery
  • The participant has fasting serum glucose <160 milligrams/deciliter (mg/dL) or below the upper limit of normal (ULN) and/or hemoglobin A1C <7%. If baseline nonfasting glucose <160 mg/dL, fasting glucose measurement is not required
  • The participant has the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • The participant has brain metastases
  • The participant has acute hepatitis
  • The participant has poorly controlled diabetes mellitus. Participants 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 participant has congestive heart failure > class II New York Heart Association (NYHA), unstable angina pectoris, new onset of angina pectoris, myocardial infarction within the past 6 months, or cardiac ventricular arrhythmias requiring antiarrhythmic therapy
  • The participant has experienced a hemorrhage or bleeding event ≥ National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 within 4 weeks prior first dose of study therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00906373


Locations
United States, Arizona
ImClone Investigational Site
Scottsdale, Arizona, United States, 85259
United States, California
ImClone Investigational Site
Los Angeles, California, United States, 90095
United States, Illinois
ImClone Investigational Site
Chicago, Illinois, United States, 60611
United States, Louisiana
ImClone Investigational Site
Metairie, Louisiana, United States, 70006
United States, Massachusetts
ImClone Investigational Site
Burlington, Massachusetts, United States, 01805
United States, New York
ImClone Investigational Site
New York, New York, United States, 10032
United States, Pennsylvania
ImClone Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00906373     History of Changes
Other Study ID Numbers: 13931
CP13-0812 ( Other Identifier: ImClone, LLC )
I5A-IE-JAEG ( Other Identifier: Eli Lilly and Company )
First Posted: May 21, 2009    Key Record Dates
Results First Posted: June 4, 2018
Last Update Posted: June 4, 2018
Last Verified: May 2018

Keywords provided by Eli Lilly and Company:
Hepatocellular Carcinoma
Liver Neoplasms
Antibodies, Monoclonal

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs