A Pilot Study of Adjuvant Valproate for Patients With High Grade Sarcomas
Adjuvant chemotherapy for high grade soft tissue sarcomas is controversial. Given the fact
that approximately 50% of patients receiving optimum treatment will recur in three years and
die of recurrence within five years, smarter adjuvant options are needed. One such treatment
option would be to "differentiate" the high grade sarcoma into a low grade sarcoma upon
recurrence. This differentiation effect will reduce the risk of subsequent death by 50% as
determined by the overall survival difference between high grade/poorly differentiated and
low grade/ well differentiated sarcomas. Given that differentiation takes place on a time
scale that is significantly longer than cytotoxic effects, the optimum time to initiate
differentiation therapy is in the adjuvant setting; when the time to disease recurrence is
measured in months to years.
The histone deacetylase inhibitor, Valproate, has been shown to promote differentiation in
myeloid malignancies when administered in standard dosing regiments. We have recently shown
that sarcomas are conceptually similar to hematopoietic malignancies, in that both represent
diseases of aberrant development in which developing cells along their respective lineages
arrest and transform at various points of differentiation. We have recently shown in vitro
that, as for acute promyelocytic leukemia, sarcomas can be reprogrammed to reenter normal
differentiation via epigenetic modulation using histone deacetylase inhibitors. It is
therefore appealing to study Valproate based differentiation therapy in the adjuvant setting
for sarcomas.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recurrence rate of lower grade sarcoma
The primary end point will be evaluated by the 3-year recurrence rate of lower grade sarcoma histopathologically (or more well differentiated as compared to the primary tumor) amongst those who experience 3-year sarcoma recurrence.
Up to 3 years
Yes
Kevin Kalinsky, MD, MS
Principal Investigator
Columbia University
United States: Food and Drug Administration
AAAD4523
NCT01010958
October 2009
October 2014
Name | Location |
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Columbia University Medical Center | New York, New York 10032 |