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Adult Primary Hepatocellular CarcinomaPhase 2NCT00083226

Doxorubicin and Bortezomib in Treating Patients With Liver Cancer

A Phase 2 study testing doxorubicin and bortezomib in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
doxorubicin and bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
Mar 2004to Aug 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must not have known bleeding diathesis, international normalized ratio (INR) > 1.5 or Partial thromboplastin time (PTT) > 1.5 x institutional ULN (required due to biopsy portion of study); use of vitamin K or fresh frozen plasma to correct values just prior to biopsy or enrollment is not allowed are not eligible

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the tumor response rate in patients with hepatocellular carcinoma (HCC).

SECONDARY OBJECTIVES:

  1. To determine other parameters of antitumor effect including time to tumor progression and overall survival in HCC patients treated with bortezomib and doxorubicin.

II. To observe toxicity profile of bortezomib and doxorubicin in patients with hepatocellular carcinoma.

III. To evaluate proteasome 20S inhibition in tumor tissue (including proteins such as p21, p27, p53, Bax and Bcl-2 which are affected by proteasome 26S) and compare them to clinical parameters using biopsy specimens obtained from patients with HCC treated with bortezomib. (Withdrawn as of 03-2007)

IV. To measure phosphorylation of IkB in tumor tissue and compare to clinical parameters using biopsy specimens obtained from patients with HCC treated with bortezomib. (Withdrawn as of 03-2007)

  1. To evaluate the effect of bortezomib on 26S proteasome activity in peripheral white blood cells (WBC's) and patient serum. Direct measurement of 26S proteasome activity as well as proteins affected by proteasome 26S and Nuclear factor kappa-B (NF-kB) will be analyzed. (Withdrawn as of 03-2007)

OUTLINE: This is a multicenter study.

Patients receive doxorubicin intravenously (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.

Being tested
doxorubicin, bortezomib
Keywords
doxorubicin, doxorubicin hydrochloride, bortezomib, hepatocellular carcinoma
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicinDrug

    Also called doxorubicin hydrochloride, ADM, ADR, Adria

    Given IV

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

Study groups in NCT00083226
Study groupRoleWhat they receive
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.
Receives: Drug: doxorubicin; Drug: bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.).

    Measured: 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)

  1. Overall Survival

    Overall survival is defined as time from registration to death from any cause. Patients alive were censored at follow up. Analysis was conducted in the 38 eligible and treated patients.

    Measured: assessed every 3 months for 2 years and then every 6 months for 1 year

  2. Progression Free Survival

    Time from registration to disease progression or death, whichever occurred earlier. Patients alive and progression-free were censored at last follow up. 36 eligible and treated patients were included in the analysis. The other 2 eligible and treated patients had no disease status information.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2004 (estimated)
  2. Study startMar 2004
  3. Primary completionFeb 2011
  4. Study completionAug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00083226
Sponsor's protocol ID
NCI-2014-00654
Other IDs
NCI-2012-02952, E6202, U10CA021115
Status last verified
Jan 2014
First submitted
14 May 2004
Last updated
30 Oct 2014
Data monitoring committee
No

Publications

  • 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.

    PubMed 24890858

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin and bortezomib in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate Measured by Response Evaluation Criteria In Solid Tumors (RECIST) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00083226, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2014.

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