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

NCT00242502 | Completed Phase 2 Results

• 1 other identifier: 2004-0874
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

Hepatocellular Carcinoma; Liver Cancer; Bevacizumab; Anti-VEGF monoclonal antibody; rhuMAb-VEGF; Erlotinib Hydrochloride; OSI-774; Tarceva; Erlotinib; Avastin

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Rate

  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.

  Baseline to 16 weeks

Study Arms (1)

Bevacizumab + Erlotinib

EXPERIMENTAL

Bevacizumab 10 mg/kg intravenous every 14 days, repeat cycle every 28 days; Erlotinib 150 mg orally every day continuous dosing.

Drug: Bevacizumab (Avastin); Drug: Erlotinib

Interventions

Bevacizumab (Avastin) DRUG

10 mg/kg IV every 14 days, repeat cycle every 28 days

Also known as: Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Bevacizumab + Erlotinib

Erlotinib DRUG

150 mg orally every day continuous dosing, repeat cycle every 28 days

Also known as: Erlotinib Hydrochloride, OSI-774, Tarceva

Bevacizumab + Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed hepatocellular carcinoma not amenable to curative resection.
• Patients must have measurable disease as per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2.
• Childs-Pugh status of A or B.
• 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).
• 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.
• Fertile men and women must agree to use adequate contraception prior to study entry and for the duration of study participation.
• 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.

You may not qualify if:

• Patients who have had prior vascular endothelial growth factor (VEGF) - or epidermal growth factor receptor (EGFR)-targeted therapy.
• History of prior malignancy other than non-melanoma skin cancer or cervical dysplasia, within five years prior to protocol entry.
• 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.
• Abnormalities of the cornea based on history (eg dry eye syndrome, Sjogren's syndrome) or congenital abnormality (eg Fuch's dystrophy).
• Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
• 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.
• Patients may not have received any other investigational agents nor have received any systemic chemotherapy \</=30 days prior to enrollment.
• 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.
• History of myocardial infarction or unstable angina within 6 months.
• History of stroke within 6 months.
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• Significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease).
• Evidence of clinically significant (Common Toxicity Criteria (CTC) Grade 3 or 4) venous or arterial thrombotic disease within previous 6 months.
• Current evidence of bleeding disorder or coagulopathy that is not controlled by conservative medical management.
• Known presence or clinical evidence of central nervous system or brain metastases.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas (UT) MD Anderson Cancer Center official website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Ahmed Kaseb, MD/ Professor
• Organization: University of Texas MD Anderson Cancer Center

MJLim@mdanderson.org

Study Officials

• Ahmed Kaseb, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2005
• First Posted: October 20, 2005
• Study Start: October 1, 2005
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: May 6, 2013
• Results First Posted: May 6, 2013

Record last verified: 2013-03

Locations

US (1)