NCT00049322

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, cisplatin, and mitomycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Monoclonal antibodies, such as bevacizumab, can kill any tumor cells that are left after chemoembolization by blocking their ability to grow and spread. PURPOSE: This randomized phase II trial is studying to see if chemoembolization followed by bevacizumab works better than chemoembolization alone in treating patients who have liver cancer that cannot be removed with surgery.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2003

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 12, 2002

Completed
3 months until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
4 months until next milestone

Study Start

First participant enrolled

June 1, 2003

Completed
8.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2012

Completed
4.1 years until next milestone

Results Posted

Study results publicly available

March 15, 2016

Completed
Last Updated

September 1, 2020

Status Verified

February 1, 2016

Enrollment Period

8.7 years

First QC Date

November 12, 2002

Results QC Date

January 20, 2016

Last Update Submit

August 17, 2020

Conditions

Keywords

localized unresectable adult primary liver cancerrecurrent adult primary liver canceradult primary hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

  • Neovessel Formation as Measured by Angiogram at 14 Weeks

    Angiograms were assessed for changes in vascularity. The numbers indicate how many subjects in each group showed neovessel formation.

    14 weeks

Secondary Outcomes (4)

  • Progression Free Survival

    16 weeks

  • Assess the Toxicities of Bevacizumab in Patients With Liver Function Impairment

    16 weeks

  • Assess Pharmakokinetics of Bevacizumab in Liver Disease

    day 85

  • Measure (Vascular Endothelial Growth Factor)VEGF Before and After TACE With and Without Bevacizumab

    21 days after TACE

Study Arms (2)

Arm I-bevacizumab

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning 1 week prior to the first chemoembolization at a dose of 10 mg/kg. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab

Arm II-chemoembolization

NO INTERVENTION

chemoembolization as part of standard of care

Interventions

bevacizumabBIOLOGICAL

Given IV, 10mg/kg evey two weeks starting 1 week prior to the first chemoembolization. Patients crossed over to the Bevacizumab arm will receive Bevacizumab after week 14 at the same dose.

Also known as: Avastin
Arm I-bevacizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \> 18 year old
  • Histologically or cytologically documented HCC
  • Patients must have bi-dimensional measurable disease by CT or MRI scan that does not exceed 50% of the liver parenchyma
  • Patients must be considered clinical candidates for chemoembolization, with at least one lesion \> 3cm and no lesion \> 15cm in its longest diameter
  • Patients awaiting cadaveric orthotopic liver transplantation are eligible if they meet all other criteria. These patients must have a model for end-stage liver disease priority score \< 28 points at entry
  • Cirrhosis Child-Pugh class A or B
  • Patients with documented grad III varices or prior history of UGI bleeding will require endoscopic evaluation prior to treatment under this protocol.
  • Platelet count equal or greater than 60,000/μL
  • Female patients must use effective contraception, be surgically sterile or be postmenopausal; male patients must be using barrier contraception or be surgically sterile
  • Patients must be willing and able to comply with all study requirements and have signed the informed consent

You may not qualify if:

  • Previous history of liver transplantation
  • Fibrolamellar histology
  • Prior antiangiogenesis therapy
  • Presence of extrahepatic disease
  • Presence of biliary obstruction defined as biliary dilatation and total bilirubin \> 2.5mg/dl
  • Thrombosis of the main portal vein
  • Absolute contraindications to doxorubicin, mitomycin-C, cisplatin, iodinated contrast material, Avitene or dexamethasone treatment
  • Other active malignancies during the past year (except for non-melanoma skin cancer or in situ carcinomas)
  • ECOG PS\> 2 or life expectancy \< 12 weeks
  • History or evidence upon physical examination of CNS disease
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure within 3 months of study entry; fine needle aspirations within 7 days prior to Day 0
  • Current or recent (within the 10 days prior to Day 0) use of full-dose oral or parenteral anticoagulants (except as required to maintain patency of preexisting, permanent indwelling IV catheters) or thrombolytic agent (for subjects receiving warfarin, international normalized ration of \< 1.5)
  • Chronic, daily treatment with aspirin (\> 325mg/day) or nonsteroidal anti-inflammatory medications
  • Positive pregnancy test or lactation
  • Proteinuria at baseline or clinically significant impairment of renal function. Subjects unexpectedly discovered to have \> 1+ proteinuria at baseline should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate \< 500 mg of protein/24 hr to allow participation in the study
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Related Publications (1)

  • Britten CD, Gomes AS, Wainberg ZA, Elashoff D, Amado R, Xin Y, Busuttil RW, Slamon DJ, Finn RS. Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: a pilot study. BMC Cancer. 2012 Jan 14;12:16. doi: 10.1186/1471-2407-12-16.

MeSH Terms

Conditions

Liver NeoplasmsCarcinoma, Hepatocellular

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesLiver DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Limitations and Caveats

Size of study limits any strong conclusions regarding efficacy.Since this study was first designed and implemented, there have been many advances in the field, including confirmation of proof of principal for anti-angiogenic agents in advanced HCC.

Results Point of Contact

Title
Carolyn Britten, M.D.
Organization
University of California Los Angeles

Study Officials

  • Carolyn Britten, MD

    Jonsson Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 12, 2002

First Posted

January 27, 2003

Study Start

June 1, 2003

Primary Completion

February 1, 2012

Study Completion

February 1, 2012

Last Updated

September 1, 2020

Results First Posted

March 15, 2016

Record last verified: 2016-02

Locations