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Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: April 14, 2009   Last Updated: June 13, 2009   History of Changes
Sponsored by: Medical University of South Carolina
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00881751
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, 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. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab, erlotinib, and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with erlotinib is more effective than giving sorafenib in treating patients with liver cancer.

PURPOSE: This randomized phase II trial is studying how well giving bevacizumab together with erlotinib works compared with sorafenib as first-line therapy in treating patients with advanced liver cancer.


Condition Intervention Phase
Liver Cancer
Biological: bevacizumab
Drug: erlotinib hydrochloride
Drug: sorafenib tosylate
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label
Official Title: A Randomized Open-Label Multi-Institution Phase II Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rate as measured by RECIST criteria [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: March 2009
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
Biological: bevacizumab
Given IV
Drug: erlotinib hydrochloride
Given orally
Arm II: Active Comparator
Patients receive oral sorafenib tosylate twice daily on days 1-28.
Drug: sorafenib tosylate
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • To estimate the median time to progression in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib hydrochloride vs sorafenib tosylate.

Secondary

  • To estimate the progression-free survival, response rate, and overall survival of these patients.
  • To evaluate the safety and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
  • Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 3 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Pathologically confirmed advanced hepatocellular carcinoma (HCC)

    • Childs-Pugh class A
    • CLIP score ≤ 5
  • Not a candidate for curative surgical resection or loco-regional therapy
  • Measurable disease as per RECIST criteria, defined as ≥ 1 previously unirradiated, bidimensionally measurable lesion ≥ 20 mm by CT scan or MRI (triphasic spiral CT scan or MRI employing a "liver protocol" image capture technique required)

    • Bone lesions, ascites, and pleural effusions are not considered measurable lesions
  • No fibrolamellar HCC
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Transaminases ≤ 5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 3.0 times ULN
  • Serum albumin > 2.5 g/dL
  • PT ≤ 1.8 times ULN

    • Prolonged INR allowed for patients who require full dose anticoagulation
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min
  • Urine protein < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
  • Able to take and absorb oral medication
  • No active infection requiring parenteral therapy
  • No known HIV or AIDS
  • No uncontrolled blood pressure (BP), defined as systolic BP ≥ 150 mm Hg and/or diastolic BP ≥ 100 mm Hg
  • No uncontrolled or significant cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • Uncontrolled angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Grade 3 cardiac valve dysfunction
    • Cardiac arrhythmia not controlled by medication
    • Stroke or transient ischemic attack within the past 6 months
    • Arterial thrombotic event of any type within the past 6 months
  • No significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease) within the past 6 months
  • No decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy not corrected by conservative measures
  • No grade 3 bleeding esophageal or gastric varices within the past 2 months

    • Prior variceal bleeding allowed provided patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months
  • No gastric varices ≥ grade 2
  • No hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past month
  • No evidence of bleeding diathesis or coagulopathy
  • No concurrent uncontrolled illness, including, but not limited to, a history of or current evidence of unexplained nephrotic syndrome or other severe illness/disease that would preclude study participation
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious, non-healing wound, active ulcer, or untreated bone fracture
  • No significant traumatic injury within the past 28 days
  • No history of allergy to bevacizumab, erlotinib hydrochloride, sorafenib tosylate, or related compounds
  • No other primary malignancy within the past 5 years, except carcinoma in situ of the cervix or urinary bladder or nonmelanoma skin cancer
  • No mental incapacitation or psychiatric illness that would preclude study participation
  • Not incarcerated or compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical illness (e.g., infectious disease)

PRIOR CONCURRENT THERAPY:

  • Prior surgery, local ablation, trans-arterial hepatic artery embolization, or trans-arterial chemoembolization are allowed provided the lesion(s) have progressed since treatment OR there are additional measurable, untreated lesions present
  • No prior systemic therapy for HCC
  • No prior organ transplantation
  • More than 7 days since prior minor surgical procedures, fine needle aspirations, or core biopsies (excluding placement of a vascular access device)
  • More than 28 days since any prior therapy
  • More than 28 days since prior and no concurrent major surgical procedure or open biopsy
  • More than 28 days since prior and no concurrent participation in another experimental drug study
  • No other concurrent anticancer or antitumor therapy, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
  • No other concurrent investigational agents
  • No concurrent warfarin (other types of anticoagulation allowed)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00881751

Locations
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Clinical Trials Office - Hollings Cancer Center at Medical Uni     843-792-9321        
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Melanie B. Thomas, MD Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: Hollings Cancer Center at Medical University of South Carolina ( Melanie B. Thomas )
Study ID Numbers: CDR0000640337, MUSC-101282, GENENTECH-AVF4481s
Study First Received: April 14, 2009
Last Updated: June 13, 2009
ClinicalTrials.gov Identifier: NCT00881751     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer

Study placed in the following topic categories:
Erlotinib
Liver Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Bevacizumab
Protein Kinase Inhibitors
Angiogenesis Inhibitors
Recurrence
Carcinoma
Liver Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Hepatocellular Carcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Carcinoma, Hepatocellular
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Liver Neoplasms
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Erlotinib
Digestive System Neoplasms
Neoplasms by Histologic Type
Growth Substances
Enzyme Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Adenocarcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 04, 2009