Skip to content

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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00365053
Enrollment
13
Registered
2006-08-17
Start date
2006-06-30
Completion date
2009-03-31
Last updated
2018-06-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma

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.

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.

Interventions

DRUGbelinostat

Given IV

OTHERlaboratory biomarker analysis

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
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

Design outcomes

Primary

MeasureTime frameDescription
Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) CommitteeUp to 3 yearsPer 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

MeasureTime frameDescription
Overall SurvivalUp to 3 yearsEstimated using the product-limit method of Kaplan and Meier.
Progression-free SurvivalUp to 3 yearsEstimated 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.
Toxicity ProfileUp to 3 yearsToxicity 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.
Apoptosis by TUNEL AssayAt baselineSummarized with contingency tables or scatterplots, and with quantitative measures of agreement.
Histone Acetylation by IHC and Western BlottingAt baseline and at 4 hours after last dose of PXD101 on day 5Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

Countries

United States

Participant flow

Participants by arm

ArmCount
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. belinostat: Given IV laboratory biomarker analysis: Correlative studies
13
Total13

Baseline characteristics

CharacteristicTreatment (Belinostat)
Age, Continuous73 years
Region of Enrollment
United States
13 participants
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
8 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
1 / 13
other
Total, other adverse events
13 / 13
serious
Total, serious adverse events
3 / 13

Outcome results

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

Time frame: Up to 3 years

ArmMeasureValue (NUMBER)
Treatment (Belinostat)Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee0 percentage of participants
Secondary

Apoptosis by TUNEL Assay

Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

Time frame: At baseline

Population: Assay data were not collected.

Secondary

Histone Acetylation by IHC and Western Blotting

Summarized with contingency tables or scatterplots, and with quantitative measures of agreement.

Time frame: At baseline and at 4 hours after last dose of PXD101 on day 5

Population: IHC data were not collected.

Secondary

Overall Survival

Estimated using the product-limit method of Kaplan and Meier.

Time frame: Up to 3 years

ArmMeasureValue (MEDIAN)
Treatment (Belinostat)Overall Survival4.5 Months
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.

Time frame: Up to 3 years

ArmMeasureValue (MEAN)
Treatment (Belinostat)Progression-free Survival1.2 Months
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.

Time frame: Up to 3 years

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Treatment (Belinostat)Toxicity ProfileGrade 4 : Sodium (Hyponatremia)0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Supraventricular arrhythmia NOS0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Albumin0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Anorexia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : AST0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Constipation0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Creatinine0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Sweating0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Hemoglobin6 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Lymphopenia1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Albumin1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Anorexia2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : AST0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Constipation2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Creatinine1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Sweating1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Dyspnea3 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Fatigue0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Glucose (hyperglycemia)6 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Hypoxia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Hypotension1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Infection2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Nausea2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Pain1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Sodium (Hyponatremia)0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 2 : Supraventricular arrhythmia NOS2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Hemoglobin0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Lymphopenia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Albumin0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Anorexia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : AST1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Constipation0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Creatinine0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Sweating0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Dyspnea1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Fatigue2 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Glucose (hyperglycemia)0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Hypoxia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Hypotension0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Infection0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Nausea0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Pain0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Sodium (Hyponatremia)3 Participants
Treatment (Belinostat)Toxicity ProfileGrade 3 : Supraventricular arrhythmia NOS1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Hemoglobin0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Lymphopenia0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Dyspnea1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Fatigue0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Glucose (hyperglycemia)0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Hypoxia1 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Hypotension0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Infection0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Nausea0 Participants
Treatment (Belinostat)Toxicity ProfileGrade 4 : Pain0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026