A Study of IMC-A12 in Combination With Sorafenib in Participants With Advanced Cancer of the Liver

NCT00906373 | Completed Phase 2 Results

• 3 other identifiers: 13931CP13-0812I5A-IE-JAEG
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 7

Brief Summary

To determine if IMC-A12 given in combination with Sorafenib is safe and effective for participants with advanced liver cancer.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Liver Neoplasms; Antibodies, Monoclonal

Outcome Measures

Primary Outcomes (1)

• 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.

  Date of first dose of study drug up PD or death up to 12 months

Secondary Outcomes (18)

• Number of Participants With Adverse Events (AEs)

  First day of treatment up to 22 months

• Pharmacokinetic (PK): Maximum Concentration (Cmax) Cycle 1

  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)

• PK: Minimum Concentration (Cmin) Cycle 1

  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)

• PK: Half-Life (t1/2) Cycle 1

  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)

• PK: Clearance (CL) Cycle 1

  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)

Study Arms (2)

Cohort 1, IMC A12 - 10 mg/kg

ACTIVE COMPARATOR

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.

Biological: IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg); Drug: Sorafenib

Cohort 2, IMC A12 20 - mg/kg

ACTIVE COMPARATOR

Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.

Biological: IMC-A12 (cixutumumab) - 20 mg/kg; Drug: Sorafenib

Interventions

IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg) BIOLOGICAL

intravenous infusions 10 mg/kg on Day 1 of each 3-week cycle

Also known as: cixutumumab, LY3012217

Cohort 1, IMC A12 - 10 mg/kg

IMC-A12 (cixutumumab) - 20 mg/kg BIOLOGICAL

intravenous infusions 20 mg/kg on Day 1 of each 3-week cycle

Also known as: cixutumumab, LY3012217

Cohort 2, IMC A12 20 - mg/kg

Sorafenib DRUG

400 milligrams (mg) twice per day orally

Cohort 1, IMC A12 - 10 mg/kg; Cohort 2, IMC A12 20 - mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (7)

ImClone Investigational Site

Scottsdale, Arizona, 85259, United States

Location

ImClone Investigational Site

Los Angeles, California, 90095, United States

Location

ImClone Investigational Site

Chicago, Illinois, 60611, United States

Location

ImClone Investigational Site

Metairie, Louisiana, 70006, United States

Location

ImClone Investigational Site

Burlington, Massachusetts, 01805, United States

Location

ImClone Investigational Site

New York, New York, 10032, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

cixutumumab; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Per the protocol efficacy analysis was only performed for Cohort 2. No PK analysis was done, the assay used for PK assessment was not reliable and the values could not be used. The samples expired before a new assay was developed.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 21, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: May 1, 2014
• Last Updated: June 4, 2018
• Results First Posted: June 4, 2018

Record last verified: 2018-05

Locations

US (7)