Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Carcinoma

Mediastinal Neoplasms

Thymoma

Thymus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Thoracic Neoplasms

Lymphatic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Belinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

1000 mg/m\^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Belinostat (PDX101)

Giuseppe Giaccone, M.D.

Background:

* Cisplatin-containing chemotherapy is the standard treatment for advanced tumors of the thymus that cannot be removed surgically.
* New treatment options are needed for patients with advanced tumors of the thymus that do not improve with cisplatin-containing therapy.
* Belinostat is a drug that inhibits enzymes called histone deacetylase. Histone deacetylase inhibitors have shown promising activity in many cancers and may be useful in treating patients with thymic tumors.

Objectives:

-To assess the safety and effectiveness of belinostat for treatment of malignant thymic tumors in patients who failed after standard treatment.

Eligibility:

-Patients 18 years of age or older with an advanced thymic tumor that has progressed after treatment with platinum-containing chemotherapy.

Design:

* Patients receive belinostat treatment in 21-day cycles. The drug is given as an infusion through a vein during days 1 through 5 of each cycle. Treatment cycles continue as long as the medicine is tolerated and the cancer does not worsen.
* Patients have a physical examination and several blood tests during every cycle.
* Patients have an electrocardiogram every cycle before starting the belinostat infusion and again on the last day of the infusion.
* Patients undergo computed tomography (CT) or other imaging test, such as ultrasound or MRI, every two cycles to evaluate the response of the tumor to treatment.
* Tumor tissue obtained from a previous biopsy is used for research purposes.

Background:

Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. Histone deacetylase inhibitors have shown promising clinical activity in many malignancies. Belinostat, a potent histone deacetylase inhibitor, is a promising agent, which may have activity in patients with thymic malignancies.

Objectives:

* To assess objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for belinostat monotherapy.
* To assess safety of belinostat.
* To evaluate time to response, duration of response, progression-free survival and overall survival.
* To identify chromosomal gains or losses and gene methylation status by comparative genomic hybridization and methylation microarrays in thymoma / thymic carcinomas in relation to clinical outcome.
* To assess expression levels of particular proteins on the pretreatment tumor sample, by immunohistochemistry (IHC) and correlate them with clinical outcome.
* To identify and measure changes in p21 and protein hyperacetylation in peripheral blood mononuclear cells (PBMC), and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in plasma and correlate them with clinical outcome.
* To measure changes in modulation of T-cell function in peripheral blood lymphocytes.

Eligibility:

* Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum containing chemotherapy regimen.
* Measurable disease by RECIST criteria.
* Adequate renal, hepatic and hematopoietic function.
* QT Interval must be less than 500 msec at baseline by electrocardiogram (EKG) (Fridericia's formula used for correction).
* No major surgery, radiotherapy, or chemotherapy within 28 days of belinostat therapy.

Design:

* Patients will receive belinostat as a 30-minute intravenous (IV) infusion of 1000 mg/m\^2/day during days 1-5 every 3 weeks. After 12 cycles of treatment, cycles will be given every 4 weeks.
* Treatment with belinostat alone will continue until disease progression.
* Toxicity will be assessed every cycle by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011.
* Tumor response assessments by RECIST criteria will be performed every 2 cycles. After 12 cycles, response assessment will be every 3 cycles.
* Correlative studies including comparative genomic hybridization, methylation microarray analysis, and tissue immunohistochemistry studies will be done on existing tumor blocks.
* Blood samples for circulating plasma biomarkers of response including VEGF will be drawn the first day of cycle 1 and 2 as well as cycle 1, day 3.
* Blood samples for protein hyperacetylation and T cell modulation analyses will be drawn the first day of cycle 1 and 2.

Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

A Multicenter Phase II Study of Belinostat (PXD-101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma

Response is defined by the Response Evaluation Criteria in Solid Tumor (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. For additional details about the RECIST criteria see the protocol Link module.

Utilize a patients tumor tissue to determine if there is any correlation between chromosomal gains or losses in comparative genomic hybridization in thymoma and thymic carcinomas and clinical outcomes.

Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

CTCAE v3.0 from beginning of study through 12/31/10; CTCAE v4.0 beginning 1/1/11.

Belinostat Treatment

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Arun Rajan, M.D.

Thymoma Patients

Thymic Patients

Number of Participants With a Partial Response

1000 mg/m\^2 day, 30 minute intravenous infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Number of Participants With Adverse Events

Unpublished data from Dr. Giaccone's lab does not reveal an association between these parameters and outcomes in patients with thymic malignancies. Hence we do not plan to perform analyses for these outcome measures and there is no known negative clinical implications associated with this.

Chromosomal Gains or Losses in Comparative Genomic Hydridization in Thymoma and Thymic Cancer

Overall Study

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Pleural Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Lung Diseases

Respiratory Tract Diseases

Pleural Diseases

Mediastinal Diseases

Thoracic Diseases

Anti-Infective Agents

Chlorotrianisene

Mitomycins

Mitomycin

Ethiodized Oil

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Patients receive lipiodol intra-arterially (IA), mitomycin IA, and embospheres IA and undergo TACE on study. Patients also undergo angiography and computed tomography (CT) at baseline and follow up.

Computed Tomography

Transarterial Chemoembolization

Tris-acryl Gelatin Microspheres

Franz E. Boas

Franz E Boas

This phase II trial evaluates how well transarterial chemoembolization (TACE) works for treating patients with non-small cell lung cancer. TACE is a minimally invasive procedure that involves injecting chemotherapy directly into an artery that supplies blood to tumors, and then blocking off the blood supply to the tumors. Mitomycin (chemotherapy), Lipiodol (drug carrier), and Embospheres (small plastic beads that block off the artery) are injected into the tumor-feeding artery. This traps the chemotherapy inside the tumor and also cuts off the tumor's blood supply. As a result, the tumor is exposed to a high dose of chemotherapy, and is also deprived of nutrients and oxygen. TACE can be effective at controlling or stopping the growth of lung tumors.

PRIMARY OBJECTIVE:

I. To determine safety and efficacy (local progression free survival) of chemoembolization of lung cancer that is chemorefractory, unresectable, and unablatable.

OUTLINE:

Patients receive lung chemoembolization using Lipiodol, mitomycin, and Embospheres. Response to treatment is evaluated on computed tomography (CT) scans.

Transarterial Chemoembolization for the Treatment of Lung Cancer

Phase II Trial of Lung Chemoembolization

Progression is determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. criteria, compared to the scan immediately prior to treatment of that territory, using the 2 largest measurable lesions per treated territory. Local progression-free survival will be estimated using the Kaplan-Meier method.

Complications will be classified using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The rate of complications can be estimated with a standard error of less than 10%. Further, any complication that occurs with a 10% incidence will be observed with greater than 95% probability.

Evaluated on a per-treatment basis, using RECIST version 1.1 criteria.

Will be estimated using the Kaplan-Meier method.

Percentage of treatments where target tumors were supplied by bronchial artery, non-bronchial systemic artery, or pulmonary artery, based on catheter angiography. Confidence intervals of proportions will be estimated using the equal-tailed Jeffreys prior interval.

Correlation between lipiodol retention and change in tumor size will be evaluated using Spearman's rank correlation coefficient (rho) and Spearman's test.

Percentage change in size (largest diameter) of the largest treated, compared to the largest untreated tumor will be evaluated using the Wilcoxon signed-rank test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage	NCT00589290	Thymoma Thymic Carcinom...	Belinostat (PDX...	18 Years -	National Institutes of Health Clinical Center (CC)
Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage	NCT00589290	Thymoma Thymic Carcinom...	Belinostat (PDX...	18 Years -	National Institutes of Health Clinical Center (CC)
Transarterial Chemoembolization for the Treatment of Lung Cancer	NCT05672108	Lung Non-Small ... Mediastinal Neo... Pleural Neoplas...	Computed Tomogr... Ethiodized Oil Mitomycin Transarterial C... Tris-acryl Gela...	18 Years -	City of Hope Medical Center

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