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Adult Primary Hepatocellular CarcinomaPhase 2NCT00365391

Bevacizumab and Erlotinib in Treating Patients With Advanced Liver Cancer

A Phase 2 study testing bevacizumab and erlotinib hydrochloride in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with advanced liver cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bevacizumab and erlotinib hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
Aug 2006to Jun 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Absolute neutrophil count >= 1,500/mm^3
  • Creatinine =< 2 mg/dL
  • Albumin >= 2.5 g/dL
  • Total bilirubin =< upper limit of normal (ULN)
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN
  • Alkaline phosphatase =< 5 times ULN
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  • Urine protein:creatinine ratio < 1.0 OR 24-hour urine protein < 1,000 mg
  • Not pregnant or nursing:
  • No nursing for >= 6 months after completion of study treatment
  • Negative pregnancy test
  • Fertile patients must use effective contraception during study and for >= 6 months after completion of study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to bevacizumab or erlotinib hydrochloride
  • No abnormalities of the cornea, including any of the following:
  • History of dry eye syndrome or Sjögren's syndrome; Congenital abnormality (e.g., Fuch's dystrophy); Abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose); Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
  • No stroke or transient ischemic attack within the past 6 months
  • No uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
  • No unstable angina pectoris within the past 6 months
  • No symptomatic congestive heart failure
  • No myocardial infarction within the past 6 months
  • No serious uncontrolled cardiac arrhythmias
  • No uncontrolled diabetes mellitus
  • No active or uncontrolled infection
  • No impaired GI function or disease that may significantly alter the absorption of erlotinib hydrochloride (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or bowel obstruction)
  • Able to swallow tablets
  • No psychiatric illness or social situation that would limit compliance with study requirements
  • No history of nephrotic-range protein
  • No history of bleeding diathesis
  • No encephalopathy
  • No serious nonhealing wounds, skin ulcers, or bone fractures
  • No clinically significant peripheral vascular disease
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of a GI bleed that required procedural intervention (e.g., variceal banding, surgical shunt, transvenous intrahepatic porto-systemic shunt [TIPS]) within the past 3 months
  • No significant traumatic injury within the past 28 days
  • No other prior malignancy within the past 5 years except for the following:
  • Adequately treated basal cell or squamous cell skin cancer; Adequately treated in situ cervical cancer; Stage I or II cancer from which the patient is currently in complete remission; Stage I chronic lymphocytic leukemia
  • Recovered from all therapy-related toxicities
  • No more than 1 prior systemic or liver directed drug therapy including transarterial chemoembolization (TACE) (multiple TACEs will count as 1 prior regimen irrespective of their total numbers) that were used for HCC
  • No chemotherapy for HCC within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • No biological therapy or immunotherapy for HCC within the past 4 weeks
  • Prior surgery, regional therapy (e.g., transarterial embolization), liver transplantation, or other liver-directed ablative therapies of discrete lesions allowed provided any related progressive or recurrent disease is documented
  • No cryotherapy, radiofrequency ablation, ethanol injection, or photodynamic therapy within the past 6 weeks:
  • Indicator lesions must be outside the area of prior treatment OR if the lesion is inside the area of prior treatment, there must be clear evidence of disease progression associated with that lesion
  • No core biopsy within the past 7 days
  • No radiotherapy within the past 4 weeks
  • No prior antiangiogenesis agent or antiepidermal growth factor receptor drug
  • No prior treatment with hepatic arterial infusion with chemotherapy or yttrium Y 90-labeled microspheres
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy
  • Concurrent full-dose anticoagulants (e.g., warfarin) with international normalized ratio (INR) > 1.2 allowed provided the following criteria are met:
  • An in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant (or on a stable dose of low molecular weight heparin)
  • AND (continued from above) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal [GI] ulceration, or known varices)
  • No concurrent major surgical procedures
  • Histologically confirmed hepatocellular carcinoma (HCC):
  • No fibrolamellar subtype HCC
  • Advanced disease
  • Not a candidate for surgical resection or liver transplantation
  • Measurable disease:
  • Edges of the indicator lesion must be clearly distinct on CT scan
  • Lesions that measure at least 1 cm but less than 2 cm only must use spiral CT imaging for both pre- and post-treatment tumor assessments
  • Child's Pugh classification A or B
  • No primary brain tumor, brain metastasis, or other central nervous system (CNS) diseases
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Platelet count >= 75,000/mm^3
  • No major surgery (e.g., laparotomy), open biopsy, or minor surgery (e.g., insertion of a vascular access device) within the past 4 weeks
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
  • No concurrent prophylactic hematopoietic colony-stimulating factors

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase II Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer (HCC)

This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with advanced liver cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and erlotinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with erlotinib may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the objective response rate in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib.

SECONDARY OBJECTIVES:

  1. Evaluate the time to progression in patients treated with this regimen. II. Evaluate the overall and progression-free survival of patients treated with this regimen.

III. Evaluate the adverse events in patients treated with this regimen.

TERTIARY OBJECTIVES:

  1. Determine the presence of epidermal growth factor receptor (EGFR) mutations in tumor tissue and correlate this with response rate, progression, and survival in patients treated with this regimen.

II. Evaluate the expression of molecules involved in EGFR signal transduction, including EGFR, phosphorylated-EGFR, Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), phosphorylated-MAPK, and HER2/neu by immunohistochemistry (from tumor tissue) and correlate these with patient outcome measures.

III. Determine the levels of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor tissue as well as baseline plasma VEGF levels and correlate these with patient outcome measures.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine epidermal growth factor receptor (EGFR) and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by immunohistochemistry (IHC) for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by enzyme-linked immunosorbent assays (ELISA).

After completion of study treatment, patients are followed periodically for up to 3 years.

Being tested
bevacizumab, erlotinib hydrochloride
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV, 10 mg/kg, days 1 and 15 in every cycle

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    Given orally, 150 mg, every day during each cycle.

Study groups in NCT00365391
Study groupRoleWhat they receive
Treatment (monoclonal antibody, enzyme inhibitor)ExperimentalPatients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
Receives: Biological: bevacizumab; Drug: erlotinib hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR).

    Responses to erlotinib and bevacizumab treatment were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters.

    Measured: Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment.

Secondary outcomes (4)

  1. Survival Time

    Survival time is defined as the time from registration to death due to any cause. Estimated using the method of Kaplan-Meier.

    Measured: From registration to death due to any cause, patients are followed up to 3 years after treatment

  2. Time to Disease Progression

    Time to disease progression is defined as the time from registration to documentation of disease progression. Estimated using the method of Kaplan-Meier.

    Measured: From registration to documentation of disease progression, up to 3 years after treatment.

  3. Duration of Response

    Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.

    Measured: The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.

  4. Time to Treatment Failure

    Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.

    Measured: From the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionAug 2008
  4. Study completionJun 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00365391
Sponsor's protocol ID
NCI-2009-00136
Other IDs
MC044I, N01CM62205
Status last verified
Mar 2013
First submitted
16 Aug 2006
Last updated
9 Jul 2015

Publications

  • Philip PA, Mahoney MR, Holen KD, Northfelt DW, Pitot HC, Picus J, Flynn PJ, Erlichman C. Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer. Cancer. 2012 May 1;118(9):2424-30. doi: 10.1002/cncr.26556. Epub 2011 Sep 27.

    PubMed 21953248

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab and erlotinib hydrochloride in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 68 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR). (time frame: Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00365391, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.

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