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

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00242502
First received: October 18, 2005
Last updated: March 25, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Hepatocellular Carcinoma
Liver Cancer
Drug: Bevacizumab (Avastin)
Drug: Erlotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Combination of Bevacizumab and Erlotinib in Patients With Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression-free Survival (PFS) Rate [ Time Frame: Baseline to 16 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 62
Study Start Date: October 2005
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

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

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.
  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: NCT00242502

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00242502     History of Changes
Other Study ID Numbers: 2004-0874
Study First Received: October 18, 2005
Results First Received: February 19, 2013
Last Updated: March 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Hepatocellular Carcinoma
Liver Cancer
Bevacizumab
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Erlotinib Hydrochloride
OSI-774
Tarceva
Erlotinib
Avastin

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

ClinicalTrials.gov processed this record on October 23, 2014