Bevacizumab and Erlotinib in Inoperable and Metastatic Hepatocellular Carcinoma

Phase 2

Completed

Conditions: Hepatocellular Carcinoma

Interventions: Drug: Bevacizumab
Drug: Erlotinib

Registration Number: NCT00287222

Lead Sponsor: University of Arkansas

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1 - Bevacizumab/Erlotinib	Bevacizumab	Subjects will be treated with bevacizumab and erlotinib
1 - Bevacizumab/Erlotinib	Erlotinib	Subjects will be treated with bevacizumab and erlotinib

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Remained Free of Progression at the 27th Week.	27 weeks

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Kansas University Medical Center
🇺🇸
Kansas City, Kansas, United States