Efficacy and Safety Study of Bevacizumab and Erlotinib to Treat Primary Liver Cancer That Cannot be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00242502
Recruitment Status : Completed
First Posted : October 20, 2005
Results First Posted : May 6, 2013
Last Update Posted : May 6, 2013
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The primary objective will be to assess progression-free survival (PFS) measured at 16 weeks following initiation of therapy with the combination of Avastin and erlotinib in patients with unresectable hepatocellular carcinoma (HCC). Progression-free survival is defined as the time from initiation of therapy until documented disease progression or death.

Secondary objectives include: response rate, median and overall survival, toxicity and tolerability, and to ascertain whether there is any correlation of response with prior treatment status and underlying HCC risk factor(s).

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Cancer Drug: Bevacizumab (Avastin) Drug: Erlotinib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the Combination of Bevacizumab and Erlotinib in Patients With Unresectable Hepatocellular Carcinoma
Study Start Date : October 2005
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Bevacizumab + Erlotinib
Bevacizumab 10 mg/kg intravenous every 14 days, repeat cycle every 28 days; Erlotinib 150 mg orally every day continuous dosing.
Drug: Bevacizumab (Avastin)
10 mg/kg IV every 14 days, repeat cycle every 28 days
Other Names:
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Drug: Erlotinib
150 mg orally every day continuous dosing, repeat cycle every 28 days
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva

Primary Outcome Measures :
  1. Progression-free Survival (PFS) Rate [ Time Frame: Baseline to 16 weeks ]
    Progression free survival (PFS) at 16 weeks of treatment with the combination of Avastin and erlotinib where participant said to be failure free at 16 weeks if they are alive, and their disease has not progressed. PFS Rate is number of participants with PFS at 16 weeks out of total participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have histologically confirmed hepatocellular carcinoma not amenable to curative resection.
  2. Patients must have measurable disease as per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
  3. Patients are allowed to have had up to one prior systemic therapy, including chemotherapy or hormonal therapy. Previous treatments that are also allowed that do not count as systemic therapy include: surgical resection, transarterial embolization/chemoembolization (TAE/TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), provided that the lesion(s) to be evaluated in this study are separate from the previously treated lesions(s). Any prior therapy must have been completed >/= 30 days prior to study entry.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
  5. Childs-Pugh status of A or B.
  6. Organ function: Absolute peripheral granulocyte count of >/= 1500 mm(3), platelet count of >/= 40,000 mm(3), hemoglobin >/= 10 gm/dL. Total bilirubin </= 2.0 gm/dL; serum albumin >/= 2.5 gm/dL; transaminases up to 5 times the upper limit of institutional normal; and prothrombin time prolonged not more than 3 seconds greater than institutional normal, once attempts to correct a prolonged PT have been made. Patients who require full dose anticoagulation, who are otherwise eligible for this trial, are allowed to have an appropriately prolonged International Normalized Ratio (INR).
  7. Negative pregnancy test in women with childbearing potential (those who are not surgically sterilized or who are not amenorrheic for >/= 12 months), within one week prior to initiation of treatment.
  8. Fertile men and women must agree to use adequate contraception prior to study entry and for the duration of study participation.
  9. Age >/= 18 years. The agents Avastin and erlotinib have not been studied in pediatric patients, thus the doses to be used in this study cannot be assumed to be safe in children.

Exclusion Criteria:

  1. Patients who have had prior vascular endothelial growth factor (VEGF) - or epidermal growth factor receptor (EGFR)-targeted therapy.
  2. History of prior malignancy other than non-melanoma skin cancer or cervical dysplasia, within five years prior to protocol entry.
  3. History of ruptured Hepatocellular carcinoma (HCC) lesion, or HCC lesion with large necrotic areas seen on conventional imaging studies, as determined by the Principal Investigator.
  4. Abnormalities of the cornea based on history (eg dry eye syndrome, Sjogren's syndrome) or congenital abnormality (eg Fuch's dystrophy).
  5. Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
  6. Uncontrolled intercurrent illness including but not limited to: ongoing or active infection requiring parenteral therapy; known HIV disease, New York Heart Association Class II or greater heart failure, cardiac arrhythmia not controlled by medication, uncontrolled psychiatric illness, a history of or current evidence of unexplained nephrotic syndrome, history of uncontrolled hypertension (defined as systolic blood pressure >140 and/or diastolic blood pressure > 90) that is refractory to medical management.
  7. Patients may not have received any other investigational agents nor have received any systemic chemotherapy </=30 days prior to enrollment.
  8. History of significant gastrointestinal bleeding requiring procedural intervention (eg variceal banding, TIPS procedure, arterial embolization) within 3 months prior to study enrollment. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened for esophageal varices. If varices are identified that require intervention (banding),patient will not be eligible until varices adequately treated.
  9. History of myocardial infarction or unstable angina within 6 months.
  10. History of stroke within 6 months.
  11. Any prior history of hypertensive crisis or hypertensive encephalopathy.
  12. Significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease).
  13. Evidence of clinically significant (Common Toxicity Criteria (CTC) Grade 3 or 4) venous or arterial thrombotic disease within previous 6 months.
  14. Current evidence of bleeding disorder or coagulopathy that is not controlled by conservative medical management.
  15. Known presence or clinical evidence of central nervous system or brain metastases.
  16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
  17. Minor surgical procedures, fine needle aspirations or core biopsies, excluding placement of a vascular access device, within 7 days prior to Day 0.
  18. Pregnant (positive pregnancy test) or lactating.
  19. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
  20. Serious, non-healing wound, ulcer, or bone fracture.
  21. Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio >/= 1.0 at screening, or: Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
  22. Known hypersensitivity to any component of Avastin
  23. Inability to comply with study and/or follow-up procedures.
  24. Radiographic evidence of major tumor thrombus in the vena cava.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00242502

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Principal Investigator: Ahmed Kaseb, M.D. M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00242502     History of Changes
Other Study ID Numbers: 2004-0874
First Posted: October 20, 2005    Key Record Dates
Results First Posted: May 6, 2013
Last Update Posted: May 6, 2013
Last Verified: March 2013

Keywords provided by M.D. Anderson Cancer Center:
Hepatocellular Carcinoma
Liver Cancer
Anti-VEGF monoclonal antibody
Erlotinib Hydrochloride

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Erlotinib Hydrochloride
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action