Classic Kaposi' s Sarcoma Clinical Trial
Official title:
Phase II Multicentric Study of Digoxin Per os in Classic or Endemic Kaposi' s Sarcoma
Classic and endemic Kaposi's sarcoma (KS) are lymph angio proliferations associated with
human herpes virus 8 (HHV8) which treatment is poorly codified. Chemotherapies give at best
30-60% of transient responses. While interferon responses are frequent, this drug is often
poorly tolerated in elderly patients. Therefore new therapies are needed. Classic KS
represents an ideal model for evaluating new drugs since patients do not receive concomitant
immunosuppressive regimens nor antiviral therapies.
Hypoxia-inducible factor 1(HIF-1 alpha) is a major regulator of solid tumor growth and
therefore a suitable target currently explored in many cancers. Moreover HIF-1 alpha enhances
HHV-8 gene expression in KS and induces lytic replication cycle. Digoxin has anti cancer
effect in vivo through HIF-alpha down regulation in several preclinical tumor models
including KS. The identification of HIF-1 alpha as a key factor in HHV8 replication prompt us
to explore inhibition of HIF-1 alpha by digoxin as a potential therapeutic approach for KS
treatment it has and consequently may down regulate HHV-8 replication in KS. This latter
approach is heightened by recent data suggesting that Digoxin has some efficacy in vitro
against others human herpes virus i.e. Herpes simplex and Cytomegalovirus (8) (9)
In this study the investigators shall evaluate the benefit and safety profile of digoxin in
classic and endemic KS (serum drug concentration of 0.6 to 1.2 ng/ml for patients <75 years
and between 0.5-0.8 ng/ml in patients older than 75 years The participants will take study
drug digoxin, for a total of 6 cycles (4 weeks/cycle).
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