Clinical trial NCT00627042: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Liver disease
Neoplasms
Liver neoplasms
Carcinoma, Hepatocellular
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-02-29
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 \[in other words (ie), blood pressure in abnormal range despite medical management\]

Primary outcomes:
measure: Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
timeFrame: 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 outcomes:
measure: Time to Progression
timeFrame: First dose to date of PD [every 3 cycles up to 18 months (1 cycle=2 weeks)]
measure: Overall Survival
timeFrame: First dose to death due to any cause up to 37.5 months
measure: Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
timeFrame: First dose to date of objective progressive disease (PD) or death up to 18 months
measure: Duration of Response
timeFrame: 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)]
measure: Number of Participants With Serum Anti-Ramucirumab Antibodies
timeFrame: Prior to dosing at baseline, Cycles 4 and 7, and 30 days after end of therapy (1 cycle=2 weeks)
measure: Number of Participants With Drug-Related Treatment-Emergent Adverse Events
timeFrame: First dose to 37.5 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: Chicago
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Metairie
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Boston
country: United States
facility: ImClone Investigational Site
state: Massachusetts
city: Burlington
country: United States
facility: ImClone Investigational Site
state: Massachusetts
city: Philadelphia
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: