PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

May 1, 2013 updated by: National Cancer Institute (NCI)

A Phase 1 Study of PXD101 in Combination With Bortezomib (PS-341) in Patients With Advanced Solid Tumors and Lymphoma

This phase I trial is studying the side effects and best dose of PXD101 and bortezomib in treating patients with advanced solid tumors or lymphomas. PXD101 and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PXD101 may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving PXD101 together with bortezomib may kill more cancer cells.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OBJECTIVES:

I. Evaluate the safety profile and determine the maximum tolerated dose of PXD101 in combination with bortezomib in patients with advanced solid tumors or lymphomas.

II. Determine the pharmacokinetics of the combination of PXD101 and bortezomib in these patients.

III. Evaluate selected biomarkers of drug effect in these patients. IV. Evaluate the activity of this regimen, in terms of objective response rate, in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1). Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-9 patients receive escalating doses of bortezomib and PXD101 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. Blood is collected at baseline and periodically during course 1 of study treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically for 4 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80217-3364
        • University of Colorado

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumor or lymphoma that is refractory to standard therapy or for which no standard therapy exists

  • No active, untreated, or symptomatic brain metastases

    • Patients with treated brain metastases are eligible provided metastasis are stable and the patient is off all steroids and anticonvulsants
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of liver metastases)
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101, bortezomib, boron, or mannitol
  • No peripheral neuropathy > grade 1

  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Psychiatric illness or social situation that would preclude study requirements

  • No significant cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • New York Heart Association class III-IV heart failure
    • Unstable angina pectoris
    • Uncontrolled hypertension
    • Condition requiring antiarrhythmic therapy
    • Ischemic or severe valvular heart disease
    • Acute ischemia or active conduction system abnormalities by ECG
  • No marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval > 500 msec), long QT syndrome, or required use of concurrent medication during PXD101 administration that may cause torsade de pointes
  • No severe medical or psychiatric problems of that would preclude study compliance
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C)
  • At least 4 weeks since prior radiotherapy and recovered
  • At least 2 weeks since prior palliative radiotherapy to sites involving < 35% of bone marrow reserve
  • At least 4 weeks since prior investigational agents
  • At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
  • No prior stem cell or bone marrow transplantation
  • No concurrent radiotherapy or immunotherapy

  • No concurrent hormonal therapy

    • Luteinizing hormone-releasing hormone agonists, selective estrogen receptor modulators, or aromatase inhibitors as chronic maintenance therapy allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PXD101 in Combination with Bortezomib (PS-341)
Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).
Other: pharmacological study
Other Names:
  • pharmacological studies
Drug: bortezomib
Other Names:
  • MLN341
  • LDP 341
  • VELCADE
Drug: belinostat
Other Names:
  • PXD101

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of PXD101 in combination with bortezomib
Time Frame: Day 21
Defined as the dose level below that which results in drug-related dose limiting toxicity (DLT) in >= 2 of 6 new patients.
Day 21
Frequency and severity of treatment-related adverse events graded per NCI CTCAE version 3.0
Time Frame: Day 21
Day 21
Changes in biological markers (p21, cleaved PARP, IkB, p65 Rel A, p-AKT, p-ERK and apoptosis) from pre- to post-treatment
Time Frame: Baseline and day 21
Baseline and day 21
Objective response rate
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Pharmacokinetics of the combination of PXD101 with bortezomib
Time Frame: Baseline, end of infusion, then 15 minutes, 30 minutes, 1, 2, 4 and 6 hours from the end of infusion (days 1 and 2)
Baseline, end of infusion, then 15 minutes, 30 minutes, 1, 2, 4 and 6 hours from the end of infusion (days 1 and 2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sue Eckhardt, University of Colorado, Denver

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 5, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 5, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 6, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 3, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 1, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI-2009-01052
  • U01CA099176 (U.S. NIH Grant/Contract)
  • COMIRB 05-0705
  • UCHSC-COMIRB-05-0705
  • UCHSC-05-0705
  • NCI-7281
  • CDR0000476293

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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