Phase II Study of Sunitinib (SU11248) in Patients With Kaposi's Sarcoma in East Africa
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load
研究概览
简要总结
Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying the side effects and how well sunitinib malate works in treating patients with Kaposi sarcoma.
详细描述
PRIMARY OBJECTIVES:
I. Determine the clinical response of sunitinib malate in patients with Kaposi sarcoma (KS) in Uganda and Kenya.
II. Compare clinical response rates in endemic versus epidemic (AIDS) KS. III. Determine the safety and tolerability of sunitinib malate in patients with endemic or epidemic (AIDS) KS.
SECONDARY OBJECTIVES:
I Monitor the impact of sunitinib malate on underlying HIV-1 and Kaposi sarcoma-associated herpesvirus (KSHV) viral infection (HIV-1 plasma RNA and KSHV cell-associated DNA).
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
- •ECOG performance status 0-1
- •Documented HIV-serostatus [HIV-seronegative (endemic KS) or HIV-seropositive (epidemic/AIDS KS)]
- •No symptomatic organ involvement, visceral crisis, or life-threatening disease (e.g., extensive or symptomatic pulmonary disease or reticuloendothelial system/hepatic involvement) for which aggressive double- or triple-drug combination chemotherapy for urgent cytoreduction is indicated (i.e., doxorubicin hydrochloride, bleomycin, and vinblastine [ABV], BV, or AV)
- •Histologically confirmed Kaposi sarcoma
- •Platelet count > 75,000/uL
- •Life expectancy >= 24 weeks
- •Absolute granulocyte count > 1,000/uL
- •Hemoglobin > 8.0 g/dL OR hematocrit > 24%
- •Serum creatinine =< 2.0 mg/dL
- •AST < 3 times normal
- •Fertile patients must use effective contraception
- •Normal clinical cardiac examination and normotensive (systolic and diastolic BP < 140/90 mm Hg) documented on at least two occasions prior to enrollment
- •Normal ECG including QTc interval < 500 msec
- •Normal echocardiogram prior to enrollment (if feasibly possible)
- •Must be able to swallow study medication
- •No acute infections [Patients with chronic infections (e.g., malaria, tuberculosis, parasitic infections, or hepatitis B or C) that may be active but under treatment are allowed provided all eligibility criteria are met]
- •At least 60 days since prior local treatment modalities (e.g., resection, cryosurgery, radiotherapy, or intralesional therapy) AND treated lesions must have clearly progressed following such therapies if the lesions are to be used as an index lesion
- •No prior systemic anticancer therapy for Kaposi sarcoma
- •Concurrent antiretroviral therapy required for HIV-seropositive patients (Patient must be on a stable regimen 8 weeks prior to study enrollment--An exception may be made for patients who have exhausted or are intolerant to all available regimens)
- •No other concurrent systemic anticancer therapy
- •Patient resides in Uganda or Kenya, East Africa
排除标准
- •Pregnant or nursing
- •Baseline diarrhea >= grade 2 by CTCAE
- •Uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or acute active infection
- •Symptomatic congestive heart failure (NYHA class III or IV heart disease)
- •Unstable angina pectoris
- •Uncontrolled intercurrent illness including, but not limited to, any of the following: 1) Cardiac arrhythmia (i.e., history of serious ventricular arrhythmia, ventricular fibrillation, or ventricular tachycardia >= 3 beats in a row OR QTc >= 500 msec) 2) Psychiatric illness or social situation that would limit compliance with study requirements
研究组 & 干预措施
Arm I
Patients receive oral sunitinib malate 50 mg once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: sunitinib malate (Drug)
Arm I
Patients receive oral sunitinib malate 50 mg once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Procedure)
Arm I
Patients receive oral sunitinib malate 50 mg once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Procedure)
结局指标
主要结局
Levels of plasma-associated HIV-1 RNA viral load and cell-associated KSHV DNA viral load
时间窗: Up to 11 months
Multivariate analysis will be performed using the Cox proportional hazards model. The effects of CD4+ lymphocyte counts, plasma HIV-1 RNA viral load and KSHV DNA level on the objective response rate will be evaluated using multivariate logistic regression.
Response rate
时间窗: Up to 11 months
The true response rate will be estimated based on the number of responses using a binomial distribution. The confidence intervals for them can be estimated using same distribution. Chi-square test or Fisher's exact test will be used to examine the difference of response rate between the two cohorts and log-rank test for the difference of survival outcomes.
Overall survival
时间窗: From the date of treatment to date of death, assessed up to 11 months
Will be estimated by Kaplan-Meier method.
Progression-free survival
时间窗: From the date of treatment to date of death or date of disease progression, assessed up to 11 months
Will be estimated by Kaplan-Meier method.
次要结局
- Changes in CD4+ and CD8+ cell counts, levels of plasma-associated HIV-1 RNA, and cell-associated KSHV DNA load(Baseline and 6 weeks)