Study of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00627042
First received: February 18, 2008
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Biological: Ramucirumab (IMC-1121B)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab [ 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)] ] [ Designated as safety issue: No ]
    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 [ Time Frame: First dose to date of PD [every 3 cycles up to 18 months (1 cycle=2 weeks)] ] [ Designated as safety issue: No ]
    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 [ Time Frame: First dose to death due to any cause up to 37.5 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: First dose to date of objective progressive disease (PD) or death up to 18 months ] [ Designated as safety issue: No ]
    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 [ 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)] ] [ Designated as safety issue: No ]
    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 [ Time Frame: Prior to dosing at baseline, Cycles 4 and 7, and 30 days after end of therapy (1 cycle=2 weeks) ] [ Designated as safety issue: No ]
  • Number of Participants With Drug-Related Treatment-Emergent Adverse Events [ Time Frame: First dose to 37.5 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 42
Study Start Date: February 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramucirumab (IMC-1121B) Biological: Ramucirumab (IMC-1121B)
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.
Other Names:
  • Ramucirumab
  • IMC-1121B
  • LY3009806

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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]
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627042

Locations
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
Boston, Massachusetts, United States, 02114
ImClone Investigational Site
Burlington, Massachusetts, United States, 01805
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00627042     History of Changes
Other Study ID Numbers: 13922, CP12-0710, I4T-IE-JVBQ
Study First Received: February 18, 2008
Results First Received: May 16, 2014
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Liver disease
Neoplasms
Liver neoplasms
Carcinoma, Hepatocellular

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

ClinicalTrials.gov processed this record on July 26, 2014