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PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: California Cancer Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00365053
  Purpose

RATIONALE: PXD101 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well PXD101 works as second-line therapy in treating patients with malignant mesothelioma of the chest that cannot be removed by surgery.


Condition Intervention Phase
Malignant Mesothelioma
Drug: belinostat
Procedure: laboratory biomarker analysis
Procedure: reverse transcriptase-polymerase chain reaction
Phase II

MedlinePlus related topics: Cancer Mesothelioma
Drug Information available for: Belinostat
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Study of PXD 101 (NSC 726630) as Second-Line Therapy for Treatment of Patients With Malignant Pleural Mesothelioma

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

Primary Outcome Measures:
  • Objective tumor response rate as measured by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival by Kaplan-Meier [ Designated as safety issue: No ]
  • Time to progression by Kaplan-Meier [ Designated as safety issue: No ]
  • Toxicity profile [ Designated as safety issue: Yes ]
  • Effect of PXD101 on apoptosis and histone acetylation as measured by TUNEL assay, immunohistochemistry, and western blot [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: June 2006
Estimated Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the objective response rate in patients with unresectable malignant pleural mesothelioma (MPM) treated with PXD101.

Secondary

  • Determine the overall survival and time to progression in these patients.
  • Assess the toxicities associated with this drug in these patients.
  • Perform molecular correlative studies on tumor tissue (optional) and peripheral blood (required) and identify potential predictive markers for response.

OUTLINE: This is a multicenter study.

Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection during course 1 of treatment for biomarker correlative studies. Fetal hemoglobin (hemoglobin F) levels are measured via reverse transcriptase-polymerase chain reaction as a potential predictive marker for response.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed malignant pleural mesothelioma (MPM) of any of the following subtypes:

    • Epithelial
    • Sarcomatoid
    • Mixed
  • Have received only 1 prior systemic chemotherapy regimen for advanced mesothelioma

    • Prior intrapleural cytotoxic agents (including bleomycin) not considered systemic chemotherapy
    • Patients who are not candidates for combination chemotherapy are eligible even if they have not received prior chemotherapy
  • Unresectable disease
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

    • The sole site of measurable disease must not be located within the radiotherapy port
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-barrier contraception for 1 week before, during, and for ≥ 2 weeks after completion of study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
  • No symptomatic congestive heart failure
  • No congestive heart failure related to primary cardiac disease
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No condition requiring anti-arrhythmic therapy
  • No uncontrolled hypertension
  • No myocardial infarction within the past 6 months
  • No ischemic or severe valvular heart disease
  • No ongoing or active infection
  • No marked baseline prolongation of QT/QTc interval
  • No repeated QTc interval > 500 msec
  • No long QT syndrome
  • No other significant cardiovascular disease
  • No other uncontrolled intercurrent illness
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior valproic acid or other known histone deacetylase (HDAC) inhibitor
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 3 weeks since prior radiation therapy
  • No concurrent medication that may cause torsade de pointes
  • 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: NCT00365053

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Contra Costa Regional Medical Center
Martinez, California, United States, 94553
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Suresh Ramalingam, MD Emory University
  More Information

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

Study ID Numbers: CDR0000489194, CCC-PHII-67, NCI-7255
Study First Received: August 16, 2006
Last Updated: October 24, 2008
ClinicalTrials.gov Identifier: NCT00365053  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
epithelial mesothelioma
sarcomatous mesothelioma
advanced malignant mesothelioma
recurrent malignant mesothelioma

Study placed in the following topic categories:
Mesothelioma
Adenoma
Recurrence
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Mesothelial

ClinicalTrials.gov processed this record on January 14, 2009