Back to resultsA Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg)
IMC-A12 (cixutumumab) - 20 mg/kg
Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Liver Neoplasms, Antibodies, Monoclonal
Eligibility 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
Sites / Locations
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Cohort 1, IMC A12 - 10 mg/kg
Cohort 2, IMC A12 20 - mg/kg
Arm Description
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.
Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
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
Number of Participants With Adverse Events (AEs)
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.
Pharmacokinetic (PK): Maximum Concentration (Cmax) Cycle 1
PK: Minimum Concentration (Cmin) Cycle 1
PK: Half-Life (t1/2) Cycle 1
PK: Clearance (CL) Cycle 1
PK: Area Under the Concentration Versus Time Curve (AUC) Cycle 1
PK: Volume of Distribution at Steady State (Vss) Cycle 1
PK: Cmax Cycle 3
PK: Cmin Cycle 3
PK: t1/2 Cycle 3
PK: CL Cycle 3
PK: AUC Cycle 3
PK: Vss Cycle 3
Percentage of Participants With Complete Response (CR) and Partial Response (PR) [Objective Response Rate (ORR)]
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.
Overall Survival (OS)
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.
Time to Disease Progression (TTP)
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.
Duration of Response (DOR)
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
The Number of Participants With Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00906373
Brief Title
A Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver
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 Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To determine if IMC-A12 given in combination with Sorafenib is safe and effective for participants with advanced liver cancer.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Liver Neoplasms, Antibodies, Monoclonal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1, IMC A12 - 10 mg/kg
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Cohort 2, IMC A12 20 - mg/kg
Arm Type
Active Comparator
Arm Description
Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
intravenous infusions 10 mg/kg on Day 1 of each 3-week cycle
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab) - 20 mg/kg
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
intravenous infusions 20 mg/kg on Day 1 of each 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
400 milligrams (mg) twice per day orally
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Date of first dose of study drug up PD or death up to 12 months
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
First day of treatment up to 22 months
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Percentage of Participants With Complete Response (CR) and Partial Response (PR) [Objective Response Rate (ORR)]
Description
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.
Time Frame
Date of first dose of study drug to PD up to 12 months
Title
Overall Survival (OS)
Description
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.
Time Frame
Date of first dose of study drug to date of death up to 22 months
Title
Time to Disease Progression (TTP)
Description
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.
Time Frame
Date of first dose of study drug to date of PD up to 12 months
Title
Duration of Response (DOR)
Description
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
Time Frame
Date of first occurrence of CR or PR to first date of PD or death up to 8 months
Title
The Number of Participants With Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)
Description
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.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
ImClone Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
ImClone Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
ImClone Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
ImClone Investigational Site
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
ImClone Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver
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