Doxorubicin and Bortezomib in Treating Patients With Liver Cancer
A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma
4 other identifiers
interventional
42
1 country
1
Brief Summary
This phase II trial is studying how well giving doxorubicin together with bortezomib works in treating patients with liver cancer. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2004
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2004
CompletedFirst Submitted
Initial submission to the registry
May 14, 2004
CompletedFirst Posted
Study publicly available on registry
May 17, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2012
CompletedResults Posted
Study results publicly available
October 30, 2014
CompletedOctober 30, 2014
January 1, 2014
6.9 years
May 14, 2004
October 24, 2014
October 24, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
Tumor response was measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.0. Objective response rate included complete response (disappearance of all tumor lesions) and partial response (At least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.).
assessed every 3 cycles while on treatment. After discontinuing treatment, assessed every 3 months for 2 years and then every 6 months for 1 year
Secondary Outcomes (2)
Overall Survival
assessed every 3 months for 2 years and then every 6 months for 1 year
Progression Free Survival
assessed every 3 cycles while on treatment. After discontinuing treatment, assessed every 3 months for 2 years and then every 6 months for 1 year.
Study Arms (1)
Treatment (doxorubicin+bortezomib)
EXPERIMENTALPatients receive doxorubicin IV over 5-15 minutes on days 1 and 8. Patients also receive bortezomib at a dose of 1.3 mg/m\^2 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.
Interventions
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have microscopically confirmed hepatocellular carcinoma not amenable to curative resection; if patients have an isolated lesion in one lobe of the liver, a liver surgeon should determine resectability; central review is not required
- Patients must have measurable disease as determined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, amenable to biopsy; patients are not mandated to allow biopsy, even though it is an important aspect of this clinical trial
- Patients with history of malignancy treated within the past 5 years are not eligible; history of carcinoma-in-situ of cervix, squamous cell cancer of skin, basal cell cancer of skin, previously treated are allowed; others are excluded as recurrence of disease may confuse response rate and/or survival endpoints
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients must not have had prior systemic chemotherapy for HCC; patients on antineoplastics for non-malignant diseases, such as methotrexate for rheumatoid arthritis, are allowed, providing patients have been off these agents for at least 4 weeks and all related toxicities have resolved to baseline
- Patients may have had prior embolization without chemotherapy; patients who have had chemoembolization are not eligible; patients may have had radiofrequency (RF) ablation, cryosurgery or ethanol injection; patients must have documented progression with the involved lesion or at least one previously untreated lesion amenable to biopsy
- Platelet count must be \>= 100,000/mm\^3 in absence of splenomegaly; platelet count must be \>= 75,000/mm\^3 with splenomegaly
- Absolute neutrophil count (ANC) must be \>= 1,500/mm\^3 in absence of splenomegaly; ANC must be =\< 1,000/mm\^3 with splenomegaly
- Alkaline phosphate (ALT) must be =\< 5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) must be =\< 5 x institutional ULN
- Bilirubin must be =\< 2 mg/dl
- Patients may not exhibit Child Pugh scale grade C cirrhosis
- Serum creatinine=\< 2.0 mg/dl
- All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
- +1 more criteria
You may not qualify if:
- Patients have baseline peripheral neuropathy \> grade 1
- Patients with history of untreated malignancy other than HCC
- Patients have had prior use of octreotide or tamoxifen as therapy for HCC
- Patients with known allergy to boron, mannitol or bortezomib
- Women are pregnant or breast-feeding (due to the uncertain effects of bortezomib in the developing fetus and young infants)
- Patients have an underlying medical condition that precludes safe participation in this clinical trial
- Patients have psychiatric illness or continued substance abuse that may impair the ability to provide informed consent or prevent safe administration of bortezomib
- Patients with ejection fraction (EF) \< 50% measured by Echocardiography (ECHO) or Multiple gated acquisition (MUGA)
- Patients on verapamil who cannot be switched to an alternative medication (due to the interaction with doxorubicin)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Eastern Cooperative Oncology Group
Boston, Massachusetts, 02215, United States
Related Publications (1)
Ciombor KK, Feng Y, Benson AB 3rd, Su Y, Horton L, Short SP, Kauh JS, Staley C, Mulcahy M, Powell M, Amiri KI, Richmond A, Berlin J. Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the Eastern Cooperative Oncology Group. Invest New Drugs. 2014 Oct;32(5):1017-27. doi: 10.1007/s10637-014-0111-8. Epub 2014 Jun 4.
PMID: 24890858DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Statistician
- Organization
- ECOG Statistical Office
Study Officials
- PRINCIPAL INVESTIGATOR
Jordan Berlin
Vanderbilt-Ingram Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2004
First Posted
May 17, 2004
Study Start
March 1, 2004
Primary Completion
February 1, 2011
Study Completion
August 1, 2012
Last Updated
October 30, 2014
Results First Posted
October 30, 2014
Record last verified: 2014-01