Chemoembolization in Treating Patients With Primary Liver Cancer or Metastases to the Liver

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00003907
First received: November 1, 1999
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor.

PURPOSE: Phase II trial to study the effectiveness of chemoembolization in treating patients who have primary liver cancer or metastases to the liver that cannot be surgically removed.


Condition Intervention Phase
Liver Cancer
Metastatic Cancer
Drug: cisplatin
Drug: doxorubicin
Drug: mitomycin
Procedure: embolization
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemoembolization in Hepatocellular Carcinoma or Neuroendocrine Hepatic Metastases: A Phase II Multi-Center Trial

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Time to Progression [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 year. ] [ Designated as safety issue: No ]
    Time to progression was defined as time from embolization to documented disease progression. Patients without documented progression were censored at the time of the last documented disease evaluation or of the last treatment ended, whichever was more recent.Disease progression was defined as significant increase in size of lesions or appearance of new metastatic lesions. Specifically, 1) >=25% increase in the area of any malignant lesions greater than 2 cm² or in the sum of the products of the individual lesions in a given organ site; 2)>=50% increase in the size of the product of diameters if only one lesion is available for measurement and was less than or equal to 2 cm² in size at the initiation of therapy; 3)>=25% increase in the sum of the liver measurements below the costal margins and xyphoid; 4)Appearance of new malignant lesions


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: Assessed every 6 weeks ] [ Designated as safety issue: No ]
    Clinical complete response was defined as complete disappearance of all clinically detectable malignant disease for at least 4 weeks. Partial response was defined as >= 50% decrease in tumor size for at least 4 weeks without increase in size of any area of known malignant disease of greater than 25%, or appearance of new areas of malignant disease. Tumor response was defined as complete response + partial response.

  • Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 year. ] [ Designated as safety issue: No ]
    Overall survival was defined as time from registration to death from any causes.


Enrollment: 50
Study Start Date: August 1999
Study Completion Date: August 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hepatocellular carcinoma
Chemoemulsion (doxorubicin, mitomycin and cisplatin) followed by embolization. The entire procedure will be repeated separately to each involved lobe beginning within 8 weeks of the last lobar chemoembolization.
Drug: cisplatin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II),
  • diaminedichloroplatinum,
  • cis-platinum,
  • platinum,
  • Platinol,
  • Platinol-AQ,
  • DDP,
  • CDDP,
  • DACP,
  • NSC 119875
Drug: doxorubicin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Adriamycin,
  • Rubex,
  • Adriamycin RDF,
  • Adriamycin PFS,
  • hydroxydaunorubicin,
  • hydroxydaunomycin,
  • ADR
Drug: mitomycin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Mutamycin,
  • mitomycin
Procedure: embolization
Immediately following delivery of the chemoemulsion, particulate embolization is performed. The particulate embolic material is prepared on a separate table or tray, using absorbable gelatin sponge (Gelfoam, Upjohn, Kalamazoo, MI), in either powder or pledget form. Approximately 1 g of this temporary occlusive agent is dissolved in 20-30 cc of full-strength contrast with 2.4 cc of absolute alcohol.
Other Names:
  • trans-arterial chemoembolization,
  • TACE
Experimental: Neuroendocrine hepatic metastases
Chemoemulsion (doxorubicin, mitomycin and cisplatin) followed by embolization. The entire procedure will be repeated separately to each involved lobe beginning within 8 weeks of the last lobar chemoembolization.
Drug: cisplatin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II),
  • diaminedichloroplatinum,
  • cis-platinum,
  • platinum,
  • Platinol,
  • Platinol-AQ,
  • DDP,
  • CDDP,
  • DACP,
  • NSC 119875
Drug: doxorubicin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Adriamycin,
  • Rubex,
  • Adriamycin RDF,
  • Adriamycin PFS,
  • hydroxydaunorubicin,
  • hydroxydaunomycin,
  • ADR
Drug: mitomycin
Doxorubicin 30 mg, mitomycin 30 mg, and cisplatin 100 mg (all in powdered form) should be dissolved in 10-15 cc of contrast agent (such as isovue or optiray).
Other Names:
  • Mutamycin,
  • mitomycin
Procedure: embolization
Immediately following delivery of the chemoemulsion, particulate embolization is performed. The particulate embolic material is prepared on a separate table or tray, using absorbable gelatin sponge (Gelfoam, Upjohn, Kalamazoo, MI), in either powder or pledget form. Approximately 1 g of this temporary occlusive agent is dissolved in 20-30 cc of full-strength contrast with 2.4 cc of absolute alcohol.
Other Names:
  • trans-arterial chemoembolization,
  • TACE

Detailed Description:

OBJECTIVES:

  • Evaluate time to progression of disease in patients with unresectable hepatocellular carcinoma or neuroendocrine hepatic metastases undergoing chemoembolization.
  • Evaluate tumor response achievable with chemoembolization in this patient population.
  • Evaluate the toxicities of this treatment in these patients.
  • Evaluate survival of these patients following this treatment.
  • Evaluate extrahepatic patterns of failure following chemoembolization, to determine whether intrahepatic progression may be forestalled and survival affected in these patients.
  • Validate a consistent method of performing chemoembolization in a multicenter setting.

OUTLINE: Patients are stratified according to disease (hepatocellular carcinoma vs neuroendocrine hepatic metastases).

Patients undergo placement of a visceral arterial catheter. Patients receive doxorubicin, mitomycin, and cisplatin as a chemoemulsion via the arterial catheter into 1 hepatic lobe only. Immediately following delivery of the chemoemulsion, particulate embolization is performed. The opposite lobe, if involved, is treated within 3-5 weeks of treatment of the initial lobe.

In the absence of unacceptable toxicity, each involved lobe is treated separately a second time, in the same sequence, beginning 8 weeks after the last lobular chemoembolization. After completion of all protocol therapy, retreatment on study of either lobe is allowed for regrowth, recurrence, or new disease, provided at least 3 months have elapsed since the initial treatment of that lobe.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 19-42 patients will be accrued for this study within 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven intrahepatic hepatocellular carcinoma or neuroendocrine tumor.
  • Unresectable.
  • Bidimensionally measurable disease by Computed Tomography (CT), Magnetic resonance imaging (MRI), or UltraSound Scanning (US) within 6 weeks of registration.
  • Evidence of patent portal vasculature by Doppler US, MRI, or angiography.
  • Serum total bilirubin < 2.0 mg/dl and serum creatinine < 2.0 mg/dl within 4 weeks of registration.
  • Absolute neutrophil count (ANC) > 2000/µl and platelets > 50,000/µl within 4 weeks of registration.
  • Expected survival of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Age >= 18 years.

Exclusion Criteria:

  • Evidence of extrahepatic disease that is likely to be life-threatening within 3 months, such as brain or symptomatic lung metastases.
  • Previous intra-arterial or intra-hepatic chemotherapy or prior systemic chemotherapy within 4 weeks.
  • Concurrent malignancy.
  • Pregnant or breast-feeding women.
  • History of life-threatening contrast allergy.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003907

  Show 37 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Keith E. Stuart, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00003907     History of Changes
Other Study ID Numbers: CDR0000067083, U10CA021115, E4298
Study First Received: November 1, 1999
Results First Received: January 7, 2013
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
adult primary hepatocellular carcinoma
liver metastases

Additional relevant MeSH terms:
Liver Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Neoplastic Processes
Pathologic Processes
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Mitomycins
Mitomycin
Doxorubicin
Cisplatin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014