Hepatocellular Carcinoma
Conditions
Keywords
Inoperable and Metastatic Hepatocellular Carcinoma
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.
Interventions
DRUGBevacizumab
15 mg/KG I.V. every 21 days
DRUGErlotinib
150 mg orally every day
Sponsors
Genentech, Inc.
University of Arkansas
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Remained Free of Progression at the 27th Week. | 27 weeks |
Countries
United States
Participant flow
Recruitment details
Recruitment Period was from 7/08/2005 to 12/17/2008. Recruitment occurred at the University of Arkansas for Medical Sciences medical oncology clinic and Kansas University Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab and Erlotinib Subjects will be treated with bevacizumab and erlotinib | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Bevacizumab and Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 11 / 21 |
Outcome results
Primary
Number of Participants Who Remained Free of Progression at the 27th Week.
Time frame: 27 weeks
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Erlotinib | Number of Participants Who Remained Free of Progression at the 27th Week. | 21 participants |
Comparison: Estimating the percentage of participants that remain free of disease progression at 27 weeks from the onset of treatment, and testing that proportion against a null-hypothesis proportion of 0.04 using the one-sided exact binomial test at 5% alpha, based upon historical data from the literature.p-value: 0.000695% CI: [10, 53]one-sided exact binomial test