Clinical trial NCT00906373: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Liver Neoplasms
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-05-21
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Date of first dose of study drug up PD or death up to 12 months
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: First day of treatment up to 22 months
measure: Pharmacokinetic (PK): Maximum Concentration (Cmax) Cycle 1
timeFrame: 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)
measure: PK: Minimum Concentration (Cmin) Cycle 1
timeFrame: 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)
measure: PK: Half-Life (t1/2) Cycle 1
timeFrame: 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)
measure: PK: Clearance (CL) Cycle 1
timeFrame: 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)
measure: PK: Area Under the Concentration Versus Time Curve (AUC) Cycle 1
timeFrame: 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)
measure: PK: Volume of Distribution at Steady State (Vss) Cycle 1
timeFrame: 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)
measure: PK: Cmax Cycle 3
timeFrame: 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)
measure: PK: Cmin Cycle 3
timeFrame: 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)
measure: PK: t1/2 Cycle 3
timeFrame: 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)
measure: PK: CL Cycle 3
timeFrame: 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)
measure: PK: AUC Cycle 3
timeFrame: 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)
measure: PK: Vss Cycle 3
timeFrame: 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)
measure: Percentage of Participants With Complete Response (CR) and Partial Response (PR) [Objective Response Rate (ORR)]
timeFrame: Date of first dose of study drug to PD up to 12 months
measure: Overall Survival (OS)
timeFrame: Date of first dose of study drug to date of death up to 22 months
measure: Time to Disease Progression (TTP)
timeFrame: Date of first dose of study drug to date of PD up to 12 months
measure: Duration of Response (DOR)
timeFrame: Date of first occurrence of CR or PR to first date of PD or death up to 8 months
measure: The Number of Participants With Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)
timeFrame: Predose, immediately prior to the first Cycle 3 and Cycle 5 infusions (3-week cycle) and 30 days after last dose of study drug
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: ImClone Investigational Site
state: Arizona
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: Burlington
country: United States
facility: ImClone Investigational Site
state: Massachusetts
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
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: