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PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00365053
Recruitment Status : Completed
First Posted : August 17, 2006
Results First Posted : December 29, 2014
Last Update Posted : June 7, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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. 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.

Condition or disease Intervention/treatment Phase
Advanced Malignant Mesothelioma Epithelial Mesothelioma Recurrent Malignant Mesothelioma Sarcomatous Mesothelioma Drug: belinostat Other: laboratory biomarker analysis Phase 2

Detailed Description:


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


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


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of PXD101 (NSC 726630) as Second-Line Therapy for Treatment of Patients With Malignant Pleural Mesothelioma
Study Start Date : June 2006
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma
Drug Information available for: Belinostat

Arm Intervention/treatment
Experimental: Treatment (belinostat)
Patients receive PXD101 IV at 1000 mg/m2 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.
Drug: belinostat
Given IV
Other Name: PXD101

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [ Time Frame: Up to 3 years ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 3 years ]
    Estimated using the product-limit method of Kaplan and Meier.

  2. Progression-free Survival [ Time Frame: Up to 3 years ]
    Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  3. Toxicity Profile [ Time Frame: Up to 3 years ]
    Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Toxicities table summarizes the observed incidence by severity and type of toxicity for toxicities that are related to treatment and greater than grade 1. Adverse events assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

  4. Apoptosis by TUNEL Assay [ Time Frame: At baseline ]
    Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

  5. Histone Acetylation by IHC and Western Blotting [ Time Frame: At baseline and at 4 hours after last dose of PXD101 on day 5 ]
    Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • WBC >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00365053

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United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Suresh Ramalingam City of Hope Medical Center
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00365053    
Other Study ID Numbers: NCI-2012-02839
N01CM62209 ( U.S. NIH Grant/Contract )
First Posted: August 17, 2006    Key Record Dates
Results First Posted: December 29, 2014
Last Update Posted: June 7, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
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Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action