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

Recurrent Malignant Mesothelioma Clinical Trial

Official title:

Phase II Study of PXD101 (NSC 726630) as Second-Line Therapy for Treatment of Patients With Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00365053
• Other study ID #: NCI-2012-02839
• Secondary ID: PHII 67N01CM6220
• Status: Completed
• Phase: Phase 2
• Start date: June 2006
• Est. completion date: March 2009

Study information

• Verified date: May 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Malignant Mesothelioma
• Epithelial Mesothelioma
• Lung Neoplasms
• Mesothelioma
• Recurrent Malignant Mesothelioma
• Sarcomatous Mesothelioma

Intervention

Drug:
• belinostat
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee	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	Up to 3 years
Secondary	Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	Up to 3 years
Secondary	Progression-free Survival	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.	Up to 3 years
Secondary	Toxicity Profile	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.	Up to 3 years
Secondary	Apoptosis by TUNEL Assay	Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.	At baseline
Secondary	Histone Acetylation by IHC and Western Blotting	Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.	At baseline and at 4 hours after last dose of PXD101 on day 5