AzTrials
AzTrials

Hepatic ComplicationsPhase 1NCT00091117

Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction

A Phase 1 study testing bortezomib and pharmacological study in people with Hepatic Complications and Malignant Neoplasm, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. This phase I trial is studying the side effects and best dose of bortezomib in treating patients with advanced cancer and liver dysfunction. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatic Complications, Malignant Neoplasm
What is being tested?
bortezomib and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
3 sitesUnited States
Study dates
Jul 2004to Mar 2013
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
  • Tumor types may include any of the following: solid tumors:
  • Non-Hodgkin's lymphoma
  • Hepatocellular carcinoma, as evidenced by liver mass, elevated alpha-fetoprotein level (>= 500 ng/mL), and positive serology for hepatitis
  • Pathological confirmation is not required
  • Confirmatory evidence for a prior Hepatitis B infection (HBsAg, HBcAb and/or HBsAb) required
Show all 47Show fewer
  • No symptomatic CNS metastases
  • Brain metastasis allowed if the following criteria are met:
  • Received prior definitive treatment (radiation and/or surgery
  • Stable disease for >= 4 weeks
  • Not currently on enzyme-inducing anticonvulsants and steroids
  • Life expectancy of at least 12 weeks
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Biliary obstruction for which a shunt has been placed allowed provided the shunt has been in place for >= 10 days AND liver function is stable, defined as 2 measurements taken >= 2 days apart that qualify the patient for the same hepatic dysfunction stratum
  • No biliary sepsis
  • Creatinine =< 1.5 mg/dL
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No New York Heart Association class III or IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • No preexisting neuropathy >= grade 2
  • No ongoing or active infection
  • No other concurrent uncontrolled illness that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance
  • More than 4 weeks since prior immunotherapy
  • More than 4 weeks since prior biologic therapy
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent immunotherapy
  • No concurrent thalidomide
  • Concurrent epoetin alfa or darbepoetin alfa for management of cancer-associated anemia allowed
  • Recovered from prior chemotherapy (not including liver function)
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No concurrent chemotherapy
  • More than 2 weeks since prior radiotherapy
  • No prior radiotherapy to > 50% of the bone marrow
  • No concurrent radiotherapy
  • More than 3 weeks since prior surgery
  • No prior bortezomib
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • Concurrent cytochrome P450 interacting agents are allowed provided they are used with caution
  • Concurrent bisphosphonate therapy allowed (e.g., pamidronate or zoledronate), except during course 1 of bortezomib administration
  • ECOG 0-2
  • Fertile patients must use effective contraception during and for 30 days after study participation

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • Wayne State University

    Detroit, Michigan, 48202

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. This phase I trial is studying the side effects and best dose of bortezomib in treating patients with advanced cancer and liver dysfunction.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the safety and tolerability of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients with mild, moderate, or severe liver insufficiency.

IV. Examine the dietary influences on bortezomib disposition and efficacy. V. Examine the influences of proteasome inhibition on CYP 450 activity.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

[Note: Patients with normal hepatic function do not receive escalating doses of bortezomib.]

Medical subject headings
Neoplasms

What participants receive

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

Study groups in NCT00091117
Study groupRoleWhat they receive
TreatmentExperimentalPatients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: bortezomib; Other: pharmacological study

What is being measured

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

  1. DLT

    Measured: 21 days

  2. MTD

    Measured: 21 days

Timeline

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

  1. First posted8 Sep 2004 (estimated)
  2. Study startJul 2004
  3. Primary completionMar 2013

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00091117
Sponsor's protocol ID
NCI-2009-00059
Other IDs
NCI-2009-00059, CDR0000383782, C-2802, C-2802, 6432, U01CA062487, U01CA062505, U01CA069853
Status last verified
Dec 2013
First submitted
7 Sep 2004
Last updated
16 Dec 2013
Results posted
No

Publications

  • LoRusso PM, Venkatakrishnan K, Ramanathan RK, Sarantopoulos J, Mulkerin D, Shibata SI, Hamilton A, Dowlati A, Mani S, Rudek MA, Takimoto CH, Neuwirth R, Esseltine DL, Ivy P. Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working Group Study NCI-6432. Clin Cancer Res. 2012 May 15;18(10):2954-63. doi: 10.1158/1078-0432.CCR-11-2873. Epub 2012 Mar 6.

    PubMed 22394984

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib and pharmacological study in people with Hepatic Complications and Malignant Neoplasm, run by National Cancer Institute (NCI) at 3 sites 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 47 inclusion and 0 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 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

DLT (time frame: 21 days). The study lists 2 primary outcomes in all. 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 NCT00091117, 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 16 Dec 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in