Cixutumumab and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01008566
First received: November 5, 2009
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Biological: cixutumumab
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Phase 1

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: First 1 month of therapy ] [ Designated as safety issue: Yes ]
    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.

  • Toxicities and tolerability of this regimen as assessed by NCI CTCAE version 4.0 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Objective response rate according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Impact of cixutumumab on biomarkers related to the IGF-1R/IGF pathway [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: August 2009
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cixutumumab, sorafenib tosylate)
Patients 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.
Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of IMC-A12 given in conjunction with standard doses of sorafenib to patients with advanced hepatocellular carcinoma (HCC).

II. To describe the toxicity and tolerance of IMC-A12 at each dose studied in combination with standard-dose sorafenib in patients with advanced HCC.

III. To evaluate the impact of IMC-A12 on biomarkers related to the IGF-1R/IGF pathway which is thought relevant to HCC progression and drug resistance.

IV. To obtain preliminary assessments of efficacy through description of progression-free survival (PFS) and objective response rate (RR).

OUTLINE: This is a multicenter, dose-escalation study of cixutumumab followed by an extended accrual phase in which patients are treated at the maximum-tolerated dose.

Patients 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.

After completion of study therapy, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and willing to sign a written informed consent document

Exclusion Criteria:

  • 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
  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: NCT01008566

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Robert O'Donnell University of California at Davis Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01008566     History of Changes
Other Study ID Numbers: NCI-2012-03186, NCI-2012-03186, CCC-PHI-64, 8155, PHI-64, 8155, N01CM00038, P30CA093373, N01CM00071
Study First Received: November 5, 2009
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

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
Antibodies
Antibodies, Monoclonal
Sorafenib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014