A Multicenter Phase II Study of Propranolol for the Treatment of Kaposi Sarcoma in Adults
概览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 -
- •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.
研究组 & 干预措施
Propranolol
Begin at 1/2 the target dose for 7 days, followed by a tolerability assessment. Patients intolerant of the half dose will discontinue treatment. Patients who tolerate the 1/2 dose will increase to the full dose for 7 days, after which tolerability will be assessed on day 8. Patients who do not tolerate the full dose will taper and then discontinue treatment. Those who continue will take the target dose for 12 weeks. At week 13 time point, tolerability and response assessment will be performed:
- Complete response or partial response: continue at the target dose.
- No response (stable disease/disease progression):dose reduction to 1/2 dose for 7 days then discontinue treatment.
Patients who stay on propranolol will undergo tolerability assessments as per the protocol. Patients found to be intolerant of propranolol, or patients who have completed 21 weeks of treatment, will undergo dose reduction to the 1/2 dose for 7 days, and then propranolol will be discontinued.
干预措施: Propranolol Hydrochloride (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Through completion of treatment (estimated to be 22 weeks)
ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) based on AMC KS Response Criteria.
次要结局
- Incidence of intolerable toxicities and treatment-emergent adverse events (TEAEs) based on CTCAE v 5.0.(From start of treatment through 30 days after completion of treatment (estimated to be 26 weeks))
- Time to recurrence or progression among responders overall.(Through completion of follow-up (estimated to be 6 months and 22 weeks))