Bevacizumab and Erlotinib in Inoperable and Metastatic Hepatocellular Carcinoma

NCT ID: NCT00287222

Last Updated: 2011-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2010-09-30

Brief Summary

The primary efficacy endpoint will be the proportion of subjects that remain free of progression at the 27th week following the onset of treatment. Secondary objectives include the subject's time in weeks from treatment onset to documented disease progression as assessed by the RECIST criteria, response rate, median and overall survival, safety and tolerability.

Detailed Description

This is a phase II study to assess the proportion of subjects that remain progression-free by the 27th week following the onset of treatment and to assess the efficacy of the combination of Bevacizumab and Erlotinib in prolonging time to progression in subjects with inoperable and metastatic hepatocellular carcinoma. Subjects will be treated with a combination of rhuMAb VEGF (Bevacizumab), in combination with Erlotinib and TTP will be assessed as per RECIST criteria. The disease will be evaluated at base line and every 9 weeks with CT scan/MRI and AFP levels. Subjects will be kept on the study till disease progression (as defined by RECIST criteria) or death.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 - Bevacizumab/Erlotinib

Subjects will be treated with bevacizumab and erlotinib

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

15 mg/KG I.V. every 21 days

Erlotinib

Intervention Type: DRUG

150 mg orally every day

Interventions

Bevacizumab

15 mg/KG I.V. every 21 days

Intervention Type: DRUG

Erlotinib

150 mg orally every day

Intervention Type: DRUG

Other Intervention Names

Avastin; Tarceva

Eligibility Criteria

Inclusion Criteria

• Subjects should have histologically or cytologically confirmed diagnosis of hepatocellular carcinoma, regardless of biopsy site.
• Subjects with a liver mass and markedly elevated AFP (>500ng/mL) are eligible.
• Subjects should not be on the liver transplantation schedule
• Subjects can have prior therapy with sorafenib (nexavar) only if the therapy was stopped due to toxicity or allergic reaction soon after starting. Subjects must have been treated for less than two weeks to be eligible.
• Radiation therapy for palliation to the areas outside the site of tumor used for measurements is permitted. If a subject has received radiation therapy to the liver, the subject id eligible if there is a new lesion or if the prior lesion has increased in size.
• Subjects who have recovered from prior surgical procedure
• Performance status of ECOG 0-2
• Measurable or evaluable disease
• Be declared unresectable or not suitable candidates for surgery
• Adequate organ functions
• Serum bilirubin <3 mg/dl, AST <5x ULN, ALT <5XULN
• Serum albumin >2.5 g/dl
• Serum creatinine < 2.0 mg/dl
• ANC >1200 MM3
• Platelet count >75,000/ml
• PT/INR < 1.5 X ULN
• Life expectancy of >3 months
• Subjects should be able to sign informed consent and be agreeing to comply with therapy and follow up.
• Negative pregnancy test in women with childbearing potential, within one week prior to initiation of treatment.
• Fertile men and women must agree to use adequate contraception prior to study entry, for the duration of study participation, and for at least 1 week after therapy.
• Age >/= 18 years. The agents Bevacizumab and Erlotinib have not been studied in pediatric subjects, thus the doses to be used in this study cannot be assumed to be safe in children.

Exclusion Criteria

• Surgically resectable disease
• Subjects with active bacterial infections
• Subjects with brain metastases
• Pregnant women (positive pregnancy test) or lactating
• No other malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the subject has been disease-free for five years.
• Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sjogren's syndrome) or congenital abnormality (e.g. Fuch's dystrophy).
• Current, recent (within 4 weeks of the first infusion of the study), or planned participation in an experimental drug study other than a Genentech-sponsored Bevacizumab/Erlotinib cancer study
• Hepatic encephelopathy (as per treating physician's evaluation)
• Uncontrolled blood Pressure >150/100 mmHg
• Unstable angina
• NYHA grade II or greater congestive heart failure
• History or myocardial infraction within 6 months
• History of stroke within 6 months
• Clinically significant peripheral vascular disease (clinically significant venous or arterial thrombotic disease).
• Evidence of bleeding diathesis or coagulopathy
• Urine protein: creatinine ratio >1.0 at screening
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture
• Inability to comply with study and/or follow-up procedures
• Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
• History of significant gastrointestinal bleeding requiring procedural intervention (e.g. variceal banding, TIPS procedure, arterial embolization, topical coagulation therapy) within six months prior to study Day 0.
• 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.
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Arkansas

OTHER

Sponsor Role: lead

Responsible Party

UAMS

Principal Investigators

Rangaswamy Govindarajan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Kansas University Medical Center

Kansas City, Kansas, United States

Countries

United States

References

Govindarajan R, Siegel E, Makhoul I, Williamson S. Bevacizumab and erlotinib in previously untreated inoperable and metastatic hepatocellular carcinoma. Am J Clin Oncol. 2013 Jun;36(3):254-7. doi: 10.1097/COC.0b013e318248d83f.

Reference Type: DERIVED

PMID: 22643560 (View on PubMed)

Other Identifiers

UARK 2005-13

Identifier Type: -

Identifier Source: org_study_id