A Multicenter Phase II Study of Belinostat (PXD-101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma
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.
- 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
- 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.
- 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.
- 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
- 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With a Partial Response
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.
Giuseppe Giaccone, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|