This is a window opportunity study of propranolol in patients with angiosarcoma. The aim of this study is to prospectively evaluate the activity of propranolol in the clinical setting as monotherapy, where the neoadjuvant setting provides a good opportunity to rapidly evaluate both the clinical response and histological response, without a significant delay in anti-cancer treatment.

A pilot neoadjuvant window of opportunity study will be performed to explore the activity of propranolol monotherapy in angiosarcoma. The study consists of a single arm. Propranolol will be administred as monotherapy in a dose of 40-80 mg 2-3 times a day, if tolerated. When patients are diagnosed, standard anti-cancer treatment will be scheduled in 6 weeks while propranolol treatment can start immediately after diagnosis and will be continued until the day the standard anti-cancer treatment is started. The duration of treatment will therefore be 3-6 weeks.

Inclusion Criteria:

1. Histological proof of angiosarcoma
2. Patients with primary, recurrent and metastasised disease are eligible;
3. Patients with a window of at least 3 weeks before surgery or systemic therapy;
4. Age ≥ 18 years;
5. Able and willing to give written informed consent;
6. WHO performance status of 0, 1 or 2;
7. Evaluable disease according to RECIST 1.1 criteria; radiologic visible disease is not obligated in patients with cutaneous angiosarcoma
8. Minimal acceptable safety laboratory values
9. ANC of ≥ 1.5 x 109 /L
10. Platelet count of ≥ 100 x 109 /L
11. Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 2.5 x ULN
12. Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
13. At least one tumor lesion accessible to safely biopsy per clinical judgement of the treating physician

Exclusion Criteria:

1. Contraindication for propranolol therapy, like severe hypotension or bradycardia, sicksinus syndrome, second or third grade heart block, cardiogenic shock, untreated heart failure, severe peripheral vascular disease asthma or other obstructive lung diseases, untreated pheochromocytoma, metabolic acidosis, prolonged fasting.
2. Current treatment with β-blockade therapy.
3. Any anticancer treatment within 30 days prior to receiving the first dose of investigational treatment; with the exception of hormonal therapy for breast cancer.
4. Concurrent treatment with an anticancer therapy: with the exception of hormonal therapy for breast cancer.
5. Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance;
6. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications;
7. Pregnancy;
8. Legal incapacity