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

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:

MedlinePlus related topics: Cancer Mesothelioma

U.S. FDA Resources

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

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

National Cancer Institute (NCI)

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, CDR0000489194
Study First Received:	August 16, 2006
Last Updated:	December 11, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial

ClinicalTrials.gov processed this record on May 16, 2013