Liver Cancer, Metastatic Cancer
Conditions
Keywords
localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma, liver metastases
Brief summary
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.
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.
Interventions
DRUGcisplatin
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).
DRUGdoxorubicin
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).
DRUGmitomycin
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).
PROCEDUREembolization
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.
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Assessed every 3 months for 2 years, then every 6 months for 3 year. | 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
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | Assessed every 6 weeks | 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 | Assessed every 3 months for 2 years, then every 6 months for 3 year. | Overall survival was defined as time from registration to death from any causes. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from ECOG membership institution between August 6, 1999 and September 15, 2006. The first patient was accrued on December 15, 1999.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 17 |
| 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. | 29 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 11 |
| Overall Study | Complicating disease | 1 | 0 |
| Overall Study | Death | 2 | 0 |
| Overall Study | ineligible or not treated | 2 | 2 |
| Overall Study | Other | 1 | 3 |
| Overall Study | Progressive disease | 4 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Hepatocellular Carcinoma | Neuroendocrine Hepatic Metastases | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 62 years | 62 years |
| Region of Enrollment United States | 17 participants | 29 participants | 46 participants |
| Sex: Female, Male Female | 4 Participants | 15 Participants | 19 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 31 / 31 |
| serious Total, serious adverse events | 18 / 18 | 30 / 31 |
Outcome results
Primary
Time to Progression
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
Time frame: Assessed every 3 months for 2 years, then every 6 months for 3 year.
Population: All eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hepatocellular Carcinoma | Time to Progression | 2.3 Months |
| Neuroendocrine Hepatic Metastases | Time to Progression | 7.2 Months |
Secondary
Overall Survival
Overall survival was defined as time from registration to death from any causes.
Time frame: Assessed every 3 months for 2 years, then every 6 months for 3 year.
Population: all eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hepatocellular Carcinoma | Overall Survival | 12.0 Months |
| Neuroendocrine Hepatic Metastases | Overall Survival | 21.2 Months |
Secondary
Tumor Response
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.
Time frame: Assessed every 6 weeks
Population: all eligible and treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hepatocellular Carcinoma | Tumor Response | 0 Proportion of participants |
| Neuroendocrine Hepatic Metastases | Tumor Response | 0.17 Proportion of participants |