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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

55

Phase

  • 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

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
Intervention / Treatment
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

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

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

National Cancer Institute (NCI)

Investigators

  • 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

March 1, 2006

Primary Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

July 5, 2006

First Submitted That Met QC Criteria

July 5, 2006

First Posted (Estimate)

July 6, 2006

Study Record Updates

Last Update Posted (Estimate)

May 3, 2013

Last Update Submitted That Met QC Criteria

May 1, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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