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Liver CancerPhase 2NCT00410956

Floxuridine and Dexamethasone as a Hepatic Arterial Infusion and Bevacizumab in Treating Patients With Primary Liver Cancer That Cannot be Removed by Surgery

A Phase 2 study testing bevacizumab, dexamethasone and floxuridine in people with Liver Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites 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

RATIONALE: Drugs used in chemotherapy, such as floxuridine and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Liver Cancer
What is being tested?
bevacizumab, dexamethasone and floxuridine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
2 sitesUnited States
Study dates
9 May 2007to 7 May 2024
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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)
  • Peripheral, cholangiolar, or cholangiocellular types
  • Mixed HCC/ICC disease allowed
  • Unresectable disease
  • Less than 70% liver involvement
  • Radiographically bidimensionally measurable disease, defined as lesion ≥ 2 cm in the greatest diameter
  • May have failed prior systemic chemotherapy or ablative therapy
  • No radiographic evidence of esophageal varices
  • No history of variceal hemorrhage
  • No occlusion of the main portal vein or the right and left portal branches
  • No clinical ascites
  • Patients ineligible for first-line MSKCC protocols for HCC are eligible for this study provided there is no clinical or radiographic evidence of extrahepatic disease
  • No metastatic disease, including CNS metastases

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 12 weeks
  • Karnofsky performance status 60-100%
  • Considered a candidate for general anesthesia and hepatic artery pump placement
  • Platelet count > 100,000/mm³
  • Albumin > 2.5 g/dL
  • Bilirubin < 1.8 mg/dL
  • WBC > 3,500/mm³
  • PTT < 1.5 times upper limit of normal
  • INR < 1.5 OR in-range INR (usually 2.0-3.0) for patients on a stable dose of therapeutic warfarin
  • Urine protein < 1+ by dipstick or urine analysis OR urine protein:creatinine ratio < 1.0
  • If proteinuria ≥ 2+ at baseline, patient must have < 1 g protein/24-hour collection
  • No concurrent disease or illness that would preclude study participation, including any of the following:
  • Hepatic encephalopathy
  • Sclerosing cholangitis
  • Gilbert's disease
  • Active infection
  • No known CNS disease
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab
  • No psychiatric illness or social situation that would preclude study compliance
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious or nonhealing active wound, ulcer, or bone fracture
  • No bleeding diathesis or coagulopathy
  • No clinically significant cardiovascular disease, including any of the following:
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 100 mm Hg on antihypertensive medications
  • New York Heart Association class II-IV congestive heart failure
  • Vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Myocardial infarction within the past 6 months
  • Symptomatic peripheral vascular disease
  • Unstable angina within the past 6 months
  • History of hypertensive crisis
  • Transient ischemic attack
  • Stroke
  • No other concurrent malignancy except localized basal cell or squamous cell skin cancer
  • Chronic hepatitis and/or cirrhosis allowed provided it is Child-Pugh class A disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 4 weeks since prior and no other concurrent experimental therapy except on a Genentech-sponsored bevacizumab cancer study
  • More than 4 weeks since prior major surgical procedure or open biopsy
  • More than 1 week since prior minor surgical procedure (e.g., core biopsy), excluding placement of a vascular access device
  • No prior external-beam radiation therapy to the liver
  • No prior floxuridine
  • No chronic daily treatment with nonsteroidal anti-inflammatory medications known to inhibit platelet function
  • No chronic daily treatment with aspirin (> 325 mg/day)
  • No concurrent or recent use of a thrombolytic agent
  • No concurrent major surgery

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase II Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Intravenous Bevacizumab (A Monoclonal Antibody to Vascular Endothelial Growth Factor-A), in Patients With Unresectable Primary Hepatic Malignancy

RATIONALE: Drugs used in chemotherapy, such as floxuridine and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy directly into the arteries around the tumor together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving floxuridine and dexamethasone as a hepatic arterial infusion together with bevacizumab works in treating patients with unresectable primary liver cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the median time to progression in patients with unresectable primary hepatic malignancy treated with hepatic arterial infusion comprising floxuridine and dexamethasone in combination with systemic bevacizumab.

Secondary

  • Determine the utility of dynamic contrast-enhanced MRI (DCE-MRI) for assessing changes in tumor perfusion before and during treatment.
  • Correlate DCE-MRI findings with radiographic tumor response.

Tertiary

  • Correlate the expression patterns of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 and their cognate ligands (including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placenta growth factor [PlGF]) with disease progression and survival after therapy.
  • Assess the pro-angiogenic activity of peripheral blood before and during treatment.
  • Assess tumors for immunohistochemical markers of hypoxia (e.g., hypoxia-inducible factor [HIF-1α], carbonic anhydrase IX [CA IX], and glucose transporters [Glut-1 and Glut-3]) for correlation with initial and treatment-related changes in perfusion and permeability, as determined by DCE-MRI.

OUTLINE: This is an open-label, nonrandomized study.

Patients undergo placement of the hepatic arterial infusion (HAI) pump and a cholecystectomy. Approximately 2 weeks later, patients receive floxuridine and dexamethasone by HAI continuously on days 1-14 and bevacizumab IV over 30-90 minutes on day 15 of course 1 and on days 1 and 15 of all subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo dynamic contrast-enhanced MRI (DCE-MRI) on days 1 and 15 of course 1 and then every 8 weeks thereafter.

Tumor and nontumor tissue is collected at the time of the HAI pump placement. Tissue is examined for the expression of vascular endothelial growth factor (VEGF)-A, -B, -C, and -D, placenta growth factor (PlGF), and VEGF receptor (VEGFR)-1, -2, and -3 by immunohistochemistry. Peripheral blood is collected at baseline and on day 1 of each course. Plasma levels of VEGF-A, -B, -C, and -D are measured by immunoenzyme techniques. Blood is also examined by flow cytometry and immunological methods and by protein extraction and analysis of VEGF and VEGFR expression (by western blot). Immunohistochemical markers of hypoxia in tissue, including hypoxia-inducible factor (HIF-1α), carbonic anhydrase IX (CA IX), glucose transporters (Glut-1 and Glut-3), and Ki-67 are assessed.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Conditions
Liver Cancer
Being tested
bevacizumab, dexamethasone, floxuridine, protein expression analysis, flow cytometry
Keywords
adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer, adult primary cholangiocellular carcinoma
Medical subject headings
Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

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

Study groups in NCT00410956
Study groupRoleWhat they receive
UNRESECTABLE PRIMARY HEPATIC MALIGNANCYExperimentalAll patients enrolled in the study will receive HAI FUDR (0.16 mg/kg X pump volume / pump flow rate), Dexamethasone (1 mg/m2/day) and IV Bevacizumab at 5mg/kg. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days post surgical placement of HAI pump; patients will receive their first treatment with Bevacizumab no sooner than 28 days post surgical placement of HAI pump.
Receives: Biological: bevacizumab; Drug: dexamethasone; Drug: floxuridine; Genetic: protein expression analysis; Other: flow cytometry; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: immunologic technique; Other: laboratory biomarker analysis; Procedure: dynamic contrast-enhanced magnetic resonance imaging

What is being measured

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

  1. Median Overall Survival

    Overall median survival from time of initiation of HAI + Bev

    Measured: Up to 36 months

  2. Median Hepatic Progression Free Survival

    Median Hepatic Progression Free Survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: Up to 36 months

  3. Median Progression Free Survival

    Median Progression Free Survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: Up to 36 months

  4. Antitumor Efficacy (Complete and Partial Response, Stable and Progressive Disease)

    Antitumor efficacy (complete and partial response, stable and progressive disease). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 36 months

Secondary outcomes (1)

  1. Number of Participants Evaluated for Toxicity as Measured by NCI Common Toxicity Criteria

    Toxicity as measured by NCI Common Toxicity Criteria

    Measured: 2 years

Timeline

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

  1. First posted13 Dec 2006 (estimated)
  2. Study start9 May 2007
  3. Primary completion7 May 2024
  4. Study completion7 May 2024

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
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00410956
Sponsor's protocol ID
06-114
Other IDs
MSKCC-06114, GENENTECH-MSKCC-06114
Status last verified
May 2024
First submitted
11 Dec 2006
Last updated
10 Dec 2024

Publications

  • Kemeny NE, Schwartz L, Gonen M, Yopp A, Gultekin D, D'Angelica MI, Fong Y, Haviland D, Gewirtz AN, Allen P, Jarnagin WR. Treating primary liver cancer with hepatic arterial infusion of floxuridine and dexamethasone: does the addition of systemic bevacizumab improve results? Oncology. 2011;80(3-4):153-9. doi: 10.1159/000324704. Epub 2011 Jun 14.

    PubMed 21677464

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, dexamethasone and floxuridine in people with Liver Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites 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?

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 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 Dec 2024). 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?

Median Overall Survival (time frame: Up to 36 months). The study lists 4 primary outcomes in all. 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 NCT00410956, 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 10 Dec 2024.

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