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

NCT00410956 | Completed Phase 2 Results

• 3 other identifiers: 06-114MSKCC-06114GENENTECH-MSKCC-06114
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Liver Cancer

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

Outcome Measures

Primary Outcomes (4)

• Median Overall Survival

  Overall median survival from time of initiation of HAI + Bev

  Up to 36 months

• 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

  Up to 36 months

• 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

  Up to 36 months

• 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.

  Up to 36 months

Secondary Outcomes (1)

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

  2 years

Study Arms (1)

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

EXPERIMENTAL

All 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.

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

Interventions

bevacizumab BIOLOGICAL

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

dexamethasone DRUG

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

floxuridine DRUG

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

protein expression analysis GENETIC

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

flow cytometry OTHER

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

immunoenzyme technique OTHER

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

immunohistochemistry staining method OTHER

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

immunologic technique OTHER

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

laboratory biomarker analysis OTHER

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

dynamic contrast-enhanced magnetic resonance imaging PROCEDURE

UNRESECTABLE PRIMARY HEPATIC MALIGNANCY

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 21677464 RESULT

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Bevacizumab; Dexamethasone; Floxuridine; Flow Cytometry; Immunoenzyme Techniques; Immunohistochemistry; Immunologic Techniques

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Immunoassay; Molecular Probe Techniques; Histocytochemistry; Histological Techniques

Results Point of Contact

• Title: Dr. William Jarnagin, MD
• Organization: Memorial Sloan Kettering Cancer Center

jarnagiw@mskcc.org

212-639-7601

Study Officials

• William R. Jarnagin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 13, 2006
• Study Start: May 9, 2007
• Primary Completion: May 7, 2024
• Study Completion: May 7, 2024
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-05

Locations

US (2)