Phase II Multicentric Study of Digoxin Per os in Classic or Endemic Kaposi' s Sarcoma (KADIG 01)

This is an interventional treatment trial for Kaposi' s Sarcoma focused on measuring Kaposi' s sarcoma, Digoxin Read More

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