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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Metastatic Cancer; Liver Cancer

Treatments: Drug: cisplatin; Drug: mitomycin; Drug: doxorubicin; Procedure: embolization

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003907

E4298 (Other Identifier)

U10CA021115 (U.S. NIH Grant/Contract)

CDR0000067083

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

50 participants in 2 patient groups

Hepatocellular carcinoma

Experimental group

Description:

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.

Treatment:

Procedure: embolization

Drug: doxorubicin

Drug: mitomycin

Drug: cisplatin

Neuroendocrine hepatic metastases

Experimental group

Description:

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.

Treatment:

Procedure: embolization

Drug: doxorubicin

Drug: mitomycin

Drug: cisplatin