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PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), October 2007
Sponsors and Collaborators: University of Colorado at Denver and Health Sciences Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00348985
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Lymphoma
Lymphoproliferative Disorder
Unspecified Adult Solid Tumor, Protocol Specific
Drug: belinostat
Drug: bortezomib
Procedure: pharmacological study
Phase I

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma
Drug Information available for: Bortezomib Belinostat
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase I Study of PXD101 in Combination With Bortezomib (PS-341) in Patients With Advanced Solid Tumors and Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Frequency and severity of treatment-related adverse events graded per NCI CTCAE version 3.0; adverse event reporting performed via AdEERS [ Designated as safety issue: Yes ]
  • Laboratory parameters and vital signs [ Designated as safety issue: No ]
  • Plasma drug levels [ Designated as safety issue: No ]
  • Biological activity of PXD101 in combination with bortezomib in tumors [ Designated as safety issue: No ]
  • Disease response [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: March 2006
Estimated Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Evaluate the safety profile and determine the maximum tolerated dose of PXD101 in combination with bortezomib in patients with advanced solid tumors or lymphomas.
  • Determine the pharmacokinetics of the combination of PXD101 and bortezomib in these patients.
  • Evaluate selected biomarkers of drug effect in these patients.
  • 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.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00348985

Locations
United States, Colorado
University of Colorado Cancer Center at UC Health Sciences Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Clinical Trials Office - University of Colorado Cancer Center     720-848-0650        
Sponsors and Collaborators
University of Colorado at Denver and Health Sciences Center
Investigators
Study Chair: S. G. Eckhardt, MD University of Colorado at Denver and Health Sciences Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
O'Bryant CL, Leong S, Camidge DR, et al.: A phase 1 study of belinostat (PXD101) in combination with bortezomib in patients with advanced solid tumors and lymphoma. [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-149, 2007.

Study ID Numbers: CDR0000476293, UCHSC-05-0705, NCI-7281, UCHSC-COMIRB-05-0705
Study First Received: July 5, 2006
Last Updated: October 16, 2008
ClinicalTrials.gov Identifier: NCT00348985  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
primary central nervous system lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult T-cell leukemia/lymphoma

Study placed in the following topic categories:
Sezary syndrome
Hodgkin's disease
Hodgkin lymphoma, adult
Cutaneous T-cell lymphoma
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Lymphoma, Follicular
Sezary Syndrome
Lymphoma, B-Cell, Marginal Zone
Mycosis Fungoides
Lymphoma, large-cell, immunoblastic
Central nervous system lymphoma, primary
Lymphoma, large-cell
Lymphoma, B-Cell
Lymphomatoid granulomatosis
Burkitt's lymphoma
Leukemia
Mycoses
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-Cell, Anaplastic
Waldenstrom macroglobulinemia
Hodgkin Disease
Lymphoma
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Lymphomatoid Granulomatosis
Immunoproliferative Disorders
Leukemia, B-cell, chronic

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009