Doxorubicin and Bortezomib in Treating Patients With Liver Cancer - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00083226

Purpose

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.

Condition	Intervention	Phase
Liver Cancer	Drug: bortezomib Drug: doxorubicin hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Bortezomib

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:

Objective response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Progression-free survival at 4.5 months [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	March 2004
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083226

Locations

United States, Georgia
Winship Cancer Institute of Emory University
Altanta, Georgia, United States, 30322
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
United States, Iowa
Mercy Medical Center - Sioux City
Sioux City, Iowa, United States, 51104
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, United States, 51101
St. Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
United States, Ohio
St. Rita's Medical Center
Lima, Ohio, United States, 45801
United States, Pennsylvania
Albert Einstein Cancer Center
Philadelphia, Pennsylvania, United States, 19141
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Jordan D. Berlin, MD	Vanderbilt-Ingram Cancer Center
Investigator:	William C. Chapman, MD	Washington University Siteman Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00083226 History of Changes
Other Study ID Numbers:	CDR0000363801, U10CA021115, ECOG-E6202
Study First Received:	May 14, 2004
Last Updated:	November 12, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:

adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer
localized unresectable adult primary liver cancer

Additional relevant MeSH terms:

Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type
Doxorubicin
Bortezomib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012