Phase II Multicentric Study of Digoxin Per os in Classic or Endemic Kaposi' s Sarcoma

Inclusion Criteria:

* Age \> 18 years \<à 80 years
* Classic or endemic histologically confirmed Kaposi's Sarcoma (KS)
* Progressive disease
* KS with more than 10 lesions or involving more than one limb segment or with involvement \>3% body surface
* KS with at least 4 lesions ≥5mm
* Patients should have at least 2 others cutaneous tumor available for repeated pharmacodynamics evaluation
* At least 4 weeks wash out for all KS specific therapies including chemotherapy and immunotherapy
* Signed informed consent

Exclusion Criteria:

* Symptomatic visceral lesions
* Eastern Cooperative Oncology Group ( ECOG) performance status \> 1
* Life expectancy of ≤ 6 months
* Patients already receiving digoxin
* hepatic dysfunction defined as serum bilirubin\>25 µm/l, transaminases \> 3.0 times the upper limit of normal (ULN) (5ULN in cases of liver metastases)
* bone marrow dysfunction defined as absolute neutrophil count\<1500/mcl, platelets\<150000/mcl or hemoglobin\<8g/dL
* renal failure with creatinine clearance\< 40ml/mn
* HIV positive, active infectious hepatitis, type A, B or C
* Uncontrolled systemic infection
* Pregnant or lactating women
* Presence of any of the following on electrocardiogram (ECG): atrial arrhythmias, including atrial fibrillation and flutter with Wolff-Parkinson-White syndrome; auricular ventricular (AV) block; heart rate \< 60 beats/minute and \> 100 beats/minute; ventricular fibrillation; ventricular tachycardia; premature ventricular contractions.
* History of or current cardiac arrythmia including sinus node disease, history of AV Block, accessory AV pathway (Wolff-Parkinson-White Syndrome), history myocardial infarction, any significant valvulopathy.
* Electrolyte imbalance (hypokalemia, hypo- or hypercalcemia, hypomagnesemia)
* Severe pulmonary disease and hypoxia
* Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, hypothyroidism or hyperthyroidism, which would, in the opinion of the investigator, make this protocol unreasonably hazardous.
* Major thoracic or abdominal surgery within the prior 3 weeks.
* GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
* Immunosuppressive regimen should not be allowed including corticosteroids
* Use of any prohibited concomitant medications:

  * the calcium channel blockers diltiazem or verapamil;
  * Class I and III cardiac arrhythmic agents (such as quinidine, amiodarone);
  * beta-blockers (such as atenolol, metoprolol);
  * indomethacin (Indocin);
  * calcium carbonate antacids (e.g., Maalox, Tums, Rolaids);
  * Calcium
  * omeprazole;
  * antidiarrheal adsorbents (kaolin and pectin);
  * antibiotics P450 inhibitors clarithromycin, erythromycin telithromycin and other P450 inhibitors./such as Ritonavir)
* Persistent Grade \>2 treatment-related toxicity from prior therapy
* History of any digoxin-related or drug induced anaphylactic reaction
* Use of any other investigational agent
* Patient without health insurance coverage
* Patient under guardianship
* Enrollment into a clinical trial within last 4 weeks