A Multicenter Phase II Study of Propranolol for the Treatment of Kaposi Sarcoma in Adults
Kaposi sarcoma (KS) lesions are initiated by endothelial cells infected with KS herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). Lesion progression is driven by abnormal angiogenesis, chronic inflammation, and uncontrolled cell proliferation. KS remains one of the most commonly diagnosed cancers in many African countries where economic constraints prevent successful treatment in most patients. Treatment outcomes in developed countries are also often unsatisfactory in HIV positive patients despite good virological and immunological responses to antiretroviral therapy. Therefore, identification of new oral, safe treatment options for treatment of KS remains a research priority. Given the known anti-angiogenic properties and based on the treatment response with other benign vascular lesions such as infantile hemangioma, propranolol is a good candidate for the treatment of KS. The hypothesis of this study is that treating patients with Kaposi sarcoma with propranolol will result in an overall response rate (complete response rate plus partial response rate) of at least 45%, and that propranolol will be safe and well tolerated in this patient population.
• 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.