Back to resultsStudy of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ramucirumab (IMC-1121B)
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Liver disease, Neoplasms, Liver neoplasms, Carcinoma, Hepatocellular
Eligibility Criteria
Inclusion Criteria:
- The participant must have histologically-confirmed, unresectable HCC
- The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (cm) with conventional techniques, or ≥ 1 cm by spiral computed tomography (CT) or magnetic resonance imaging (MRI)], as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Target lesion(s) must not lay within a previously irradiated, ablated, or chemoembolized area. If a target 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 a Cancer of the Liver Italian Programme (CLIP) score of 0-3
- The participant has a Child-Pugh Classification score of A or B (liver dysfunction)
- The participant has provided signed informed consent
Exclusion Criteria:
- The participant has received prior systemic chemotherapy, biologic or anti-angiogenic therapy, or investigational systemic therapy for HCC
- The participant has had bleeding from esophageal or gastric varices during the 3 months prior to study participation. Note: If the participant has any history of known esophageal varices, or evidence of esophageal varices on CT/MRI, the participant must undergo endoscopic evaluation prior to study entry (minimally invasive capsule esophageal endoscopy is an acceptable initial modality). The participant with endoscopically detected esophageal varices is eligible provided he/she meets all other entry criteria. The participant with any history or current evidence of esophageal varices must receive oral beta-blocker therapy throughout participation while on study, he/she may receive optimal endoscopic therapy as determined by the consulting gastroenterologist or hepatologist, and must undergo regular endoscopic follow-up throughout participation while on study
- The participant has acute hepatitis
- The participant has central nervous system (CNS) metastases or carcinomatous meningitis
- The participant has poorly-controlled hypertension [in other words (ie), blood pressure in abnormal range despite medical management]
Sites / Locations
- 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 Type
Experimental
Arm Label
Ramucirumab (IMC-1121B)
Arm Description
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
PFS was defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who were alive and without disease progression and participants who did not progress and were subsequently lost to follow-up were censored at the last objective tumor assessment.
Secondary Outcome Measures
Time to Progression
The time from first day of therapy to the first date of objective evidence of progressive disease (PD) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of new lesion. Time to PD was censored at the date of death or study discontinuation.
Overall Survival
Overall survival (OS) was the duration from first dose to death due to any cause. OS was censored at last contact date for participants who were alive at the end of follow-up period or lost to follow-up.
Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
Objective response rate (ORR) was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). As classified according to Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of non-target lesions. PR was having at least a 30% decrease in sum of longest diameter of target lesions.
Duration of Response
Duration of response was the interval from the date of initial documented response [complete response (CR) or partial response (PR)] to the first documented date of disease progression, initiation of other (or additional) antitumor therapy was first reported, or death due to any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target lesions, PR was having at least a 30% decrease in the sum of the longest diameter of target lesions, and disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data were censored for participants who did not progress or die.
Number of Participants With Serum Anti-Ramucirumab Antibodies
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered by the investigator to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Full Information
NCT ID
NCT00627042
First Posted
February 18, 2008
Last Updated
September 29, 2014
Sponsor
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00627042
Brief Title
Study of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy
Official Title
An Open Label, Multicenter, Phase 2 Study Evaluating the Safety and Efficacy of IMC-1121B as First Line Monotherapy in Patients With Unresectable Hepatocellular Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (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
A study to determine how long ramucirumab (IMC-1121B) will stop cancer from growing in participants with liver cancer that cannot be treated with surgery.
Detailed Description
Inhibition of angiogenesis is considered a promising approach to the treatment of cancer. Members of the vascular endothelial growth factor (VEGF) family and the VEGF receptor-2 (VEGFR-2) are important mediators of angiogenesis and are likely important therapeutic targets in advanced hepatocellular cancer (HCC).
Angiogenesis appears integral to HCC development and pathogenesis. Angiogenesis inhibition has been efficacious in both in vitro and in vivo HCC models and results of clinical studies also suggest potential to inhibit disease growth.
Ramucirumab is a fully human monoclonal antibody (MAb) that specifically binds to the extracellular domain of VEGFR-2 with high affinity. Phase 1 studies currently nearing completion have demonstrated safety and tolerability at clinically relevant doses, with preliminary evidence of clinical efficacy in a variety of human cancers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Liver disease, Neoplasms, Liver neoplasms, Carcinoma, Hepatocellular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ramucirumab (IMC-1121B)
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Ramucirumab (IMC-1121B)
Other Intervention Name(s)
Ramucirumab, IMC-1121B, LY3009806
Intervention Description
Participants will receive ramucirumab (IMC-1121B) at 8 milligrams per kilogram (mg/kg) administered over 1 hour every other week (every 14 days). Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
Description
PFS was defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who were alive and without disease progression and participants who did not progress and were subsequently lost to follow-up were censored at the last objective tumor assessment.
Time Frame
First dose to date of progressive disease or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]
Secondary Outcome Measure Information:
Title
Time to Progression
Description
The time from first day of therapy to the first date of objective evidence of progressive disease (PD) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of new lesion. Time to PD was censored at the date of death or study discontinuation.
Time Frame
First dose to date of PD [every 3 cycles up to 18 months (1 cycle=2 weeks)]
Title
Overall Survival
Description
Overall survival (OS) was the duration from first dose to death due to any cause. OS was censored at last contact date for participants who were alive at the end of follow-up period or lost to follow-up.
Time Frame
First dose to death due to any cause up to 37.5 months
Title
Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
Description
Objective response rate (ORR) was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). As classified according to Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of non-target lesions. PR was having at least a 30% decrease in sum of longest diameter of target lesions.
Time Frame
First dose to date of objective progressive disease (PD) or death up to 18 months
Title
Duration of Response
Description
Duration of response was the interval from the date of initial documented response [complete response (CR) or partial response (PR)] to the first documented date of disease progression, initiation of other (or additional) antitumor therapy was first reported, or death due to any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target lesions, PR was having at least a 30% decrease in the sum of the longest diameter of target lesions, and disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data were censored for participants who did not progress or die.
Time Frame
Time of first response (CR or PR) to disease progression, or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]
Title
Number of Participants With Serum Anti-Ramucirumab Antibodies
Time Frame
Prior to dosing at baseline, Cycles 4 and 7, and 30 days after end of therapy (1 cycle=2 weeks)
Title
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Description
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered by the investigator to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame
First dose to 37.5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The participant must have histologically-confirmed, unresectable HCC
The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (cm) with conventional techniques, or ≥ 1 cm by spiral computed tomography (CT) or magnetic resonance imaging (MRI)], as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Target lesion(s) must not lay within a previously irradiated, ablated, or chemoembolized area. If a target 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 a Cancer of the Liver Italian Programme (CLIP) score of 0-3
The participant has a Child-Pugh Classification score of A or B (liver dysfunction)
The participant has provided signed informed consent
Exclusion Criteria:
The participant has received prior systemic chemotherapy, biologic or anti-angiogenic therapy, or investigational systemic therapy for HCC
The participant has had bleeding from esophageal or gastric varices during the 3 months prior to study participation. Note: If the participant has any history of known esophageal varices, or evidence of esophageal varices on CT/MRI, the participant must undergo endoscopic evaluation prior to study entry (minimally invasive capsule esophageal endoscopy is an acceptable initial modality). The participant with endoscopically detected esophageal varices is eligible provided he/she meets all other entry criteria. The participant with any history or current evidence of esophageal varices must receive oral beta-blocker therapy throughout participation while on study, he/she may receive optimal endoscopic therapy as determined by the consulting gastroenterologist or hepatologist, and must undergo regular endoscopic follow-up throughout participation while on study
The participant has acute hepatitis
The participant has central nervous system (CNS) metastases or carcinomatous meningitis
The participant has poorly-controlled hypertension [in other words (ie), blood pressure in abnormal range despite medical management]
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
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
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
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
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy
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