Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving doxorubicin together with bortezomib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin together with bortezomib works in treating patients with liver cancer.

Further Study Information

OBJECTIVES:

Primary

• Determine the tumor response rate in patients with hepatocellular carcinoma treated with doxorubicin and bortezomib.

Secondary

• Determine other parameters of antitumor effect, including time to tumor progression and overall survival, in patients treated with this regimen.

• Determine the toxicity profile of this regimen in these patients.

• Compare proteasome 20S inhibition in tumor tissue (including proteins such as p21, p27, p53, Bax, and Bcl-2, that are affected by proteasome 26S) with clinical parameters using biopsy specimens from patients treated with bortezomib.

• Determine phosphorylation of IkB in tumor tissue of patients treated with bortezomib.

• Compare phosphorylation of IkB in tumor tissue with clinical parameters using biopsy specimens obtained from patients treated with bortezomib.

• Determine the effect of bortezomib on 26S proteasome activity in peripheral white blood cells and serum of these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin IV over 5-15 minutes on days 1 and 8. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no disease progression may continue to receive bortezomib alone in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 13 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Microscopically confirmed hepatocellular carcinoma (HCC) not amenable to curative surgery

• Measurable disease amenable to biopsy

• Patients must have documented progression with the involved lesion OR at least one prior untreated lesion amenable to biopsy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3 (without splenomegaly) OR ≥ 1,000/mm^3 (with splenomegaly)

• Platelet count ≥ 100,000/mm^3 (without splenomegaly) OR ≥ 75,000/mm^3 (with splenomegaly)

• No known bleeding diathesis

Hepatic

• AST ≤ 5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 5 times ULN

• Bilirubin ≤ 2.0 mg/dL

• INR ≤ 1.5*

• PTT ≤ 1.5 times ULN*

• No Child-Pugh scale class C cirrhosis NOTE: *No vitamin K or fresh frozen plasma to correct laboratory values just prior to biopsy or study enrollment

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• Ejection fraction ≥ 50% by echocardiogram or MUGA

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No known allergy to boron, mannitol, or bortezomib

• No peripheral neuropathy > grade 1

• No history of other untreated malignancy

• No underlying medical condition that would preclude study participation

• No psychiatric illness or continued alcohol abuse that would preclude study compliance and giving informed consent

• No other malignancy within the past 5 years except carcinoma in situ of the cervix or previously treated squamous cell or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic hematopoietic growth factors

Chemotherapy

• No prior systemic chemotherapy for HCC

• No prior chemoembolization

• At least 4 weeks since prior antineoplastics for non-malignant disease (e.g., methotrexate for rheumatoid arthritis) and recovered

Endocrine therapy

• No prior tamoxifen for HCC

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Prior embolization (without chemotherapy), ethanol injection, radiofrequency ablation, or cryosurgery allowed

• No prior octreotide for HCC

• No concurrent verapamil

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Jordan D. Berlin

Study Chair

William C. Chapman, MD

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00083226
Information obtained from ClinicalTrials.gov on December 14, 2011

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