Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Doxorubicin and Bortezomib in Treating Patients With Liver Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	ECOG-E6202 E6202, NCT00083226

Special Category: NCI Web site featured trial

Objectives

Primary

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

Secondary

1. Determine other parameters of antitumor effect, including time to tumor progression and overall survival, in patients treated with this regimen.
2. Determine the toxicity profile of this regimen in these patients.
3. 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.
4. Determine phosphorylation of IkB in tumor tissue of patients treated with bortezomib.
5. Compare phosphorylation of IkB in tumor tissue with clinical parameters using biopsy specimens obtained from patients treated with bortezomib.
6. Determine the effect of bortezomib on 26S proteasome activity in peripheral white blood cells and serum of these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³ (without splenomegaly) OR ≥ 1,000/mm³ (with splenomegaly)
• Platelet count ≥ 100,000/mm³ (without splenomegaly) OR ≥ 75,000/mm³ (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

Expected Enrollment

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

Outcomes

Objective response rate

Overall survival
Time to progression
Toxicity
Progression-free survival at 4.5 months

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.

Berlin JD, Powell ME, Su Y, et al.: Bortezomib (B) and doxorubicin (dox) in patients (pts) with hepatocellular cancer (HCC): A phase II trial of the Eastern Cooperative Oncology Group (ECOG 6202) with laboratory correlates. [Abstract] J Clin Oncol 26 (Suppl 15): A-4592, 2008.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Jordan Berlin, MD, Protocol chair		Ph: 615-322-4967; 800-811-8480 Email: jordan.berlin@vanderbilt.edu
William Chapman, MD, Protocol co-chair		Ph: 314-362-7792; 800-600-3606

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma
Trial Start Date		2004-03-19
Trial Completion Date		2008-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00083226
Date Submitted to PDQ		2004-03-25
Information Last Verified		2008-10-22
NCI Grant/Contract Number		CA21115

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