RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have hepatocellular carcinoma (liver cancer) that cannot be removed with surgery.

Condition	Treatment or Intervention	Phase
adult primary hepatocellular carcinoma advanced adult primary liver cancer localized unresectable adult primary liver cancer recurrent adult primary liver cancer	Drug: bortezomib  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the proportion of confirmed tumor responses in patients with hepatocellular carcinoma treated with bortezomib.

Secondary

• Determine the confirmed and objective response rate in patients treated with this drug.
• Determine the duration of response, time to disease progression, and survival of patients treated with this drug.
• Determine the adverse event rate in patients treated with this drug.
• Correlate laboratory correlates with outcome (e.g., p53 and disease progression) in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 22-55 patients will be accrued for this study within 9-19 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular carcinoma
• Not amenable to surgical resection
• Tumor amenable to post-treatment biopsy
• Measurable disease
• Patients with only lesions measuring > 1 cm to ≤ 2 cm must have all tumor assessments made by spiral CT scan
• Indicator lesion(s) outside the area of prior treatment
• If the sole indicator lesion is inside the prior treatment area, there must be clear evidence of disease progression associated with that lesion
• Edges of the indicator lesion must be clearly distinct by CT scan
• Child-Pugh classification A or B
• Pre-treatment tumor tissue available
• No known CNS metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 24 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 5 times ULN
• Albumin ≥ 2.5 g/dL
• PT/INR ≤ 1.5* NOTE: *INR range of 2-3 allowed for patients on full-dose anticoagulants provided the patient has been on a stable dose of warfarin or low molecular weight heparin for ≥ 2 weeks

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant traumatic injury within the past 3 weeks
• No grade 1 or greater sensory peripheral neuropathy OR grade 1 with neuropathic pain of any etiology
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to bortezomib
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness that would limit study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent immunotherapy
• No concurrent colony-stimulating factors during the first course of study therapy

Chemotherapy

• More than 6 weeks since prior chemoembolization
• No prior systemic chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy
• More than 6 weeks since prior radiofrequency ablation
• No concurrent radiotherapy

Surgery

• More than 3 weeks since prior major surgery

Other

• More than 6 weeks since prior cryotherapy
• More than 6 weeks since prior ethanol injection
• More than 6 weeks since prior photodynamic therapy
• No prior systemic anticancer therapy
• No prior bortezomib
• No other concurrent investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States
District of Columbia
      Howard University Cancer Center at Howard University Hospital, Washington,  District of Columbia,  20060,  United States
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

George P. Kim, MD,  Study Chair,  Mayo Clinic - Jacksonville   

Study ID Numbers:  CDR0000350328; MAYO-MC0255; NCI-6139; NCT00077441
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  February 10, 2004
ClinicalTrials.gov Identifier:  NCT00077441
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08