Cixutumumab and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer
A Phase I Trial of Escalating Doses of the Anti-IGF-1R Monoclonal Antibody IMC-A12 and Standard Dose Sorafenib for Treatment of Advanced Hepatocellular Carcinoma
7 other identifiers
interventional
21
1 country
6
Brief Summary
This phase I trial is studying the side effects and best dose of cixutumumab when given together with sorafenib tosylate in treating patients with advanced liver cancer. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab together with sorafenib tosylate may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2009
CompletedFirst Submitted
Initial submission to the registry
November 5, 2009
CompletedFirst Posted
Study publicly available on registry
November 6, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2016
CompletedMay 12, 2016
May 1, 2016
6.8 years
November 5, 2009
May 11, 2016
Conditions
Outcome Measures
Primary Outcomes (2)
MTD defined as the highest IMC-A12 dose tested in which none or only one patient had a dose-limiting toxicity (DLT) attributed to IMC-A12 as assessed by NCI CTCAE version 4.0
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
First 1 month of therapy
Toxicities and tolerability of this regimen as assessed by NCI CTCAE version 4.0
30 days
Secondary Outcomes (3)
Impact of cixutumumab on biomarkers related to the IGF-1R/IGF pathway
From baseline to up to 5 years
Objective response rate according to RECIST
Up to 5 years
Progression-free rate according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 5 years
Study Arms (1)
Treatment (cixutumumab, sorafenib tosylate)
EXPERIMENTALPatients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22 and oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given orally
Eligibility Criteria
You may qualify if:
- Unresectable or metastatic HCC for which standard curative measures do not exist; the diagnosis of hepatocellular carcinoma should be based on at least one of the following:
- The presence of one or more liver lesions, measuring ≥ 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection
- The presence of liver lesion(s) with AFP \>= 400
- Tissue confirmation in the absence of a and/or b
- Tissue availability is desired and will be sought, but tissue availability is not mandated for accrual to the study
- No prior systemic therapy for HCC; patients may have had prior embolization, chemoembolization, intra-arterial chemotherapy infusion, ethanol injection, radiofrequency ablation or cryosurgery
- ECOG 0 or 1
- Life expectancy of greater than 3 months
- Absolute neutrophil count \> 1,000/mm\^3
- Platelets \> 65,000/mm\^3
- Total bilirubin =\< 2 x the institutional upper normal limit
- AST and ALT =\< 5 x the institutional upper normal limit
- Renal function =\< 1.5 mg/dl or calculated creatinine clearance \> 50 mL/min (Cockcroft-Gault formula)
- PT \< 4 seconds of prolongation above the upper normal limit
- No evidence of encephalopathy in the last 6 months
- +2 more criteria
You may not qualify if:
- Local therapy for HCC within 4 weeks prior to treatment on this study or those who have not recovered from adverse events related to therapy administered more than 4 weeks earlier
- Receiving other investigational agents
- Brain metastases, because of their poor prognosis, proclivity for progressive neurologic dysfunction that would confound the evaluation of neurologic adverse events, and the potential for increased risk for CNS adverse events
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this clinical trial
- HIV-positive patients are ineligible
- Fasting blood glucose \> 160 mg/dL
- Esophageal or gastric variceal bleeding within the last 6
- Clinically evident ascites (minimal, medically controlled ascites detectable on imaging studies only is allowed)
- Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points
- Patients unable to swallow the sorafenib tablets whole are ineligible; (the tablets cannot be crushed or broken)
- Cardiac: symptomatic congestive heart failure, unstable angina, clinically significant and uncontrolled cardiac dysrhythmia, uncontrolled hypertension (systolic BP \> 150 or diastolic BP \> 100 on two occasions within two weeks of beginning therapy on this protocol, myocardial infarction within 6 months, NYHA class \> II, LVEF \< normal as assessed on MUGA
- Fibrolamellar carcinoma or any mixed variants of HCC with fibrolamellar histology
- Hypersensitivity to human IgG unless the patient has subsequently tolerated IgG agents
- Patients with active hepatitis B infection should be on adequate antiviral therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Penn State Hershey Cancer Institute-Clinical Trials Office
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert O'Donnell
University of California, Davis
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2009
First Posted
November 6, 2009
Study Start
August 1, 2009
Primary Completion
May 1, 2016
Last Updated
May 12, 2016
Record last verified: 2016-05