Inclusion Criteria:
* Pediatric (\< 18 years) and adult (≥ 18 years) participants with biopsy-proven and measurable Kaposi Sarcoma (KS) as defined in the KS Manual of Procedures (MOP).
* No urgent clinical indication for immediate cytotoxic chemotherapy. Participants who have received cytotoxic chemotherapy \> 4 weeks prior to screening are eligible.
* KS stage:
* \< 18 years:
* 1A (Mild): disease limited to skin, flat oral mucosal lesions, and/or flesh colored subcutaneous nodules, total \<10 lesions.
* 1B (Moderate): having any of the following features, alone or in combination: a total of 10-19 hyperpigmented skin/oral lesions, nodular oral involvement, conjunctival eye involvement, or exophytic mass.
* ≥ 18 years:
* T0: confined to skin and/or lymph nodes and/or minimal oral lesions.
* T1: limited to tumor-associated edema of cutaneous lesions without functional impairment or flat oral lesions.
* Performance Status:
* \< 18 years:
* Lansky performance status \> 70%
* ≥ 18 years:
* Easter Cooperative Oncology Group (ECOG) performance status ≤ 2
* Participants must have adequate organ function, as defined by the following:
* Bilirubin (direct or total) within normal range, or total bilirubin \<3.0 mg/dl for participants with Gilbert syndrome.
* Calculated creatinine clearance ≥ 30 mL/min for participants ≥ 12 years (see Appendix III); creatinine \<1.5 Upper Limit Normal (ULN) for participants \< 12 years.
* Hemoglobin \> 9 g/dL;
* Platelets \> 100 × 109/L;
* ANC \> 1000 cells/mm3
* Human Immunodeficiency Virus (HIV) positive participants must be on antiretroviral therapy (ART) that conforms to local standards of care. Participants will have been on ART for at least 12 weeks. Participants will not be excluded based on CD4 count or HIV viral load.
* HIV positive participants must not show recent improvement on ART that may confound response evaluation:
* If on ART 12 to 24 weeks, participants 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 eight weeks.
* HIV-negative participants must not show evidence of improvement in the three months prior to enrollment.
* No history of asthma or diabetes mellitus (as it is a risk factor for hypoglycemia).
* No clinically significant cardiovascular disease other than hypertension, which is permitted.
* No use of beta-adrenergic antagonists for other indications.
* Not pregnant or planning to become pregnant. Propranolol is United Stats Food and Drug Administration (US FDA) pregnancy category C. At this time, the study team has determined that the unknown risk to a developing fetus is greater than the potential benefit of treatment.
* Use of effective contraception for women of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months.
* Women of child bearing potential (WOCBP) must agree to use adequate contraception (oral contraceptive pills, intrauterine device, Nexplanon, Depo-Provera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) prior to study entry, for the duration of study participation.
* Not breast feeding.
Exclusion Criteria:
• Participants who do not fulfill the criteria as listed in Section 3.1 above, are ineligible. Additionally, the presence of any of the following conditions will exclude a participant from study enrollment:
* Children and adolescents with lymph node or visceral disease, woody edema, or ≥ 20 cutaneous lesions.
* Children and adolescents with heart rate or systolic blood pressure \<10th percentile for age.
* Adults with visceral disease or tumor-associated edema causing functional impairment.
* Shortness of breath, hemoptysis, or moderate/severe cough not attributable to causes other than KS.
* Bleeding from the mouth or rectum not attributable to causes other than KS.
* Treatment for active and serious infection.
* Children with severe acute malnutrition based on World Health Organization (WHO) criteria (Mid-upper arm circumference \<11.5 cm, weight-for height Z-score \<-3 or presence of symmetrical pitting edema).
* Given the risk of hypotension and hypoglycemia, participants must take the study drug with food. If needed, the study team will pursue additional funding to support providing supplemental food for participants who experience food insecurity.
* Patients who experienced hypersensitivity to propranolol during initiation phase of treatment or had previous known allergy to propranolol or allergy to other β-blockers.
* Patients with a history of uncompensated heart failure; severe sinus bradycardia; sick sinus syndrome; or heart block greater than first-degree.
* Patients with diagnosed obstructive airway disease such as asthma, chronic obstructive pulmonary disease (COPD), or bronchiolitis.
* History of diabetes mellitus (as it is a risk factor for hypoglycemia)
* Patients receiving concurrent treatment with an anticancer therapy. Patients must not have received any anticancer therapies within 30 days prior to receiving the first dose of investigational treatment.
* Patients with concern for Kaposi Sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome.
