A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic Malignancies
- New options for the treatment of patients with advanced thymoma and thymic carcinoma
- Belinostat, N-hydroxy-3-(phenylsulphamoylphenyl) acrylamide, is a hydroxamic acid
deacetylase inhibitor that is able to inhibit both HDAC Class I and II enzymes.
- An ongoing phase II study of belinostat in recurrent or metastatic thymic malignancies
has shown activity which warrants further consideration of belinostat in the first
- Belinostat alterations in target protein levels due to gene expression changes may
allow increased sensitivity of cancer cells to conventional chemotherapy.
- In the Phase I portion the primary objective will be to determine a safe and tolerable
phase 2 dose, DLTs and preliminary activity for the combination of belinostat by
continuous IV infusion (CIVI) with cisplatin, doxorubicin and cyclophosphamide in
patients with advanced thymic malignancies.
- In the Phase II portion the primary objective will be to determine the clinical
response rate (PR+CR) of belinostat in combination with cisplatin, doxorubicin and
cyclophosphamide in the first line treatment of patients with advanced thymic
- To determine time to response, duration of response, progression free survival (PFS)
and overall survival (OS).
- To determine the toxicity profile and safety of this combination.
- To assess exploratory correlative markers in relation to response to treatment
(immunohistochemistry and array CGH)
- Patients with histologically confirmed advanced thymic malignancies who are
chemotherapy na ve.
- Measurable disease by RECIST criteria
- Adequate renal, hepatic and hematopoietic function
- The Phase I portion of the study will consist of four dose levels and dose escalations
will follow according to traditional 3 patient cohorts.
- Once the maximum tolerated doe is determined, the phase II portion of the study will
- Belinostat will be given as a 48h CIVI starting on day 1, doxorubicin as a slow IV
injection on days 2 and 3, cisplatin will be infused over 1 hour on day 2 and
cyclophosphamide as a slow IV infusion on Day 3.
- Treatment will be given every 21 days for no more than 6 cycles or until disease
progression. Treatment with belinostat alone may continue until disease progression.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Ph I portion - to determine a safe and tolerable phase 2 dose, DLTs and preliminary activity for the combo of belinostat by continuous IV infusion (CIVI) w/cisplatin, doxorubicin and cyclophosphamide in patients w/advanced thymic malignancies.
Arun Rajan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|