Inclusion Criteria:
* Biopsy proven Kaposi Sarcoma that is measurable with a millimeter ruler. Patients presenting for both front-line therapy and subsequent-line therapy will be considered.
* Must have two lesions greater than or equal to 4 mm x 4 mm, or one lesion greater than or equal to 8 mm x 8 mm, that are accessible for 4-mm punch biopsy. The patient must have at least 5 more lesions in addition to the lesion(s) being biopsied.
* At least 18 years of age.
* Weight ≥40 kg
* ECOG performance status ≤ 2
* Meets the appropriate HIV-related criteria:
* If HIV positive, patient must be on antiretroviral therapy (ART) that conforms to local standards of care for at least 12 weeks. HIV positive patients will not be excluded based on CD4 count or HIV viral load.
* If on ART 12 to 24 weeks, must show evidence of KS progression requiring further systemic treatment.
* If on ART for \> 24 weeks, must show no evidence of regression in the last 8 weeks.
* If HIV negative, must not show evidence of improvement in the 12 weeks prior to enrollment.
* Propranolol is US FDA pregnancy category C. For this reason, women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for one month after completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, s/e must inform her treating physician immediately.
* Able to take an oral pill.
* Ability to understand and willingness to sign an IRB approved written informed consent document.
Exclusion Criteria:
* Visceral disease causing functional impairment. Unless it is a minor, self-limiting (not affecting normal activities) condition.
* Urgently clinically indicated for immediate cytotoxic chemotherapy. Patients who have received cytotoxic chemotherapy \> 4 weeks prior to screening are eligible.
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
* Currently taking beta-andrenergic antagonist(s) for other indications. Prior use is allowed if the last dose of the beta-andrenergic antagonist is ≥ 5 half-lives of the agent prior to Day -7.
* Currently receiving concurrent treatment with an anticancer therapy. Patients must not have received any anticancer therapies within 4 weeks prior to receiving the first dose of propranolol.
* Currently receiving any other investigational agents.
* A history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to propranolol.
* History of asthma or current diagnosis of obstructive airway disease such as asthma, COPD, or bronchiolitis. Patients with mild or well-controlled obstructive airway disease may be included as long as they have not had an acute episode in the last 3 mos requiring more than 4 days/mo of treatment, change of chronic treatment, or visit to medical personnel for treatment of asthma, COPD, or bronchiolitis.
* History of diabetes mellitus, as defined by any of the following: A random blood glucose value of at least 200 mg/dL in the presence of hyperglycemia symptoms (weight loss, blurry vision, thirst, polyuria), fasting plasma glucose value of at least 126 mg/dL, A1c value of at least 7.0%, or two hour plasma glucose value of at least 200 mg/dL during a 75 g oral glucose tolerance test.
* History of uncompensated heart failure, severe sinus bradycardia (heart rate persistently \<50 beats per minute), sick sinus syndrome, or heart block greater than first degree. Patients with isolated bradycardia may be included as long as the heart rate is at least 51 beats per minute and is asymptomatic.
* History of hypotension (systolic blood pressure \<90 mmHg or mean arterial pressure \<65 mmHg) or orthostasis (\>20 mmHg fall in systolic pressure or \>10 mmHg fall in diastolic pressure with standing). (Isolated instances of hypotension may not be exclusionary after discussion with PI.)
* Shortness of breath, hemoptysis, or moderate/severe cough not attributable to causes other than KS. Patients may be included if they have a minor, self-limiting condition and their O2 sat is persistently greater than 90% and there is no hemoptysis or cough severe enough to limit normal activities.
* Bleeding from the mouth or rectum not attributable to causes other than KS. Unless it is a minor, self-limiting condition, such as blood tinged toilet paper.
* Uncontrolled intercurrent illness including, but not limited to: ongoing clinically significant active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
* Concern for KSHV inflammatory cytokine syndrome. Patients with history of prior KSHV inflammatory cytokine syndrome may be included.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 21 days of study entry.
* Evidence of untreated chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with active HBV infection can be enrolled as long as they are receiving HBV treatment. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
