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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 has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00365053
First received: August 16, 2006
Last updated: June 17, 2013
Last verified: June 2013
  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. 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 Intervention Phase
Advanced Malignant Mesothelioma
Epithelial Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Drug: belinostat
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective tumor response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Toxicity profile as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity. Toxicity will be monitored on an ongoing basis according to guidelines based on the sequential probability ratio test.

  • Apoptosis by TUNEL assay [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

  • Histone acetylation by IHC and Western blotting [ Time Frame: At baseline and at 4 hours after last dose of PXD101 on day 5 ] [ Designated as safety issue: No ]
    Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.


Enrollment: 37
Study Start Date: June 2006
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (belinostat)
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.
Drug: belinostat
Given IV
Other Name: PXD101
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365053

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Suresh Ramalingam Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00365053     History of Changes
Other Study ID Numbers: NCI-2012-02839, PHII 67, N01CM62209
Study First Received: August 16, 2006
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Belinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014