临床试验/NCT01016730

NCT01016730已完成1 期

Single-Arm, Dose-Finding Pilot Trial of Single-Agent Bortezomib in Patients With Relapsed/Refractory AIDS-Associated Kaposi Sarcoma With Correlative Assessments of KSHV and HIV

National Cancer Institute (NCI)9 个研究点分布在 1 个国家目标入组 24 人开始时间: 2010年1月22日最近更新: 2018年2月20日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 24
试验地点: 9
主要终点: MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

详细描述

PRIMARY OBJECTIVES:

I. Estimate the maximum tolerated dose (MTD) of single agent bortezomib in subjects with AIDS-related Kaposi sarcoma (KS).

SECONDARY OBJECTIVES:

I. Evaluate the clinical response of KS tumors to bortezomib. II. Evaluate the impact of bortezomib on human immunodeficiency virus (HIV) plasma viral loads and peripheral blood mononuclear cells (PBMC) apolipoprotein B messenger ribonucleic acid (mRNA) editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) levels.

III. Determine the impact of bortezomib on Kaposi's sarcoma-associated herpesvirus (KSHV).

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

•Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy
•Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion >= 12 mm or 3 >= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated
•Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria
•Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA
•Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
•Absolute neutrophil count (ANC) >= 1,000/mm^3; subjects may be receiving growth factor support to meet these criteria
•Hemoglobin >= 8.0 gm/dL; subjects may be receiving growth factor support to meet these criteria
•Platelets >= 100,000/mm^3
•Total bilirubin =< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal
•Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
•Serum creatinine =< institutional ULN or creatinine clearance >= 50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional ULN
•Pre-existing grade 3 or 4 peripheral neuropathy

排除标准

•KS that is improving in the 4 weeks prior to enrollment
•Symptomatic visceral KS (oral and lymph node involvement is eligible)
•Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities of daily living is allowable
•Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
•Expected survival < 3 months with standard KS treatments (i.e., radiation, paclitaxel)
•Concurrent active opportunistic infection (OI)
•Herpes zoster (shingles) outbreak within the last 6 months or inability to take herpes zoster prophylaxis
•Patient is =< 5 years free of another primary malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if the other primary malignancy is a localized squamous or basal cell skin cancer or cervical/anal carcinoma in situ
•Acute treatment for an infection or other serious medical illness within 14 days prior to study entry
•Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including chemotherapy, radiation therapy, biological therapy, or investigational therapy) within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment
•Prior treatment with bortezomib or other investigational proteasome inhibitors
•Previous local therapy of any KS indicator lesion within 60 days, unless the lesion has clearly progressed with enlargement since the local therapy
•Use of any investigational drug or treatment within 4 weeks prior to randomization
•Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance
•Hypersensitivity to boron
•Subjects with grade III/IV cardiac disease as defined by the New York Heart Association criteria. (e.g., congestive heart failure, myocardial infarction within 6 months of study)
•Subject has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis); subjects with known hepatitis B or C infection may be enrolled if they have either documentation of no or minimal fibrosis on liver biopsy or undetectable hepatitis virus on polymerase chain reaction (PCR)
•Systemic corticosteroid treatment, other than replacement doses
•Female subjects who are pregnant or breast-feeding

研究组 & 干预措施

Treatment (bortezomib)

Experimental

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

干预措施: Bortezomib (Drug)

Treatment (bortezomib)

Experimental

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

干预措施: Laboratory Biomarker Analysis (Other)

Treatment (bortezomib)

Experimental

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

干预措施: Questionnaire Administration (Other)

结局指标

主要结局

MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

时间窗: 56 days

MTD is defined as the highest assigned dose at which \< 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.

次要结局

Changes in bortezomib in KSHV copy number in PBMC and plasma(Baseline to 1 year)
Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels(Baseline to 1 year)
Changes in viral antigen expression in biopsy specimens(Baseline to 1 year)
Change in lytic gene expression(Baseline to 1 year)
Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors(Up to 1 year)

研究者

发起方

National Cancer Institute (NCI)

申办方类型

Nih

责任方

Sponsor

研究点 (9)

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