A Phase I Study of HS-196, an HSP90 Inhibitor-linked Near Infrared Probe for Detection of Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Fluorescence
研究概览
简要总结
HS-196 is near infrared red (NIR)-tethered HSP90 inhibitor for clinical imaging of selective tumor binding. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.
详细描述
The product to be tested under this IND, HS-196, is a tumor imaging agent.
Hsp90 (heat shock protein 90) is a chaperone protein that aids in the folding, stabilization, and degradation of cellular proteins and is found in virtually all living organisms. Cancer cells in particular have high expression of Hsp90. Hsp90 has three structural domains including an N-terminal domain that contains an ATP binding site. Small molecule inhibitors of HSP90 (Hsp90i) can selectively and competitively to the Hsp90 ATP binding domain. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.
HS-196 will be used in this investigation for the imaging of solid tumors The objectives of the study are to determine the dose of HS-196 that achieves the greatest ratio of tumor to normal tissue fluorescence in patients with malignancy, the safety of HS-196 administration in patients with malignancy, the average radiant efficiency in resected tumors following HS-196 administration, the localization of the HS-196 by microscopy of tumor slices, and the PK metrics of HS-196 when administered to patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For Dose escalation and recommended dose phases:
- •Diagnosis of a solid malignancy, stage I-IV, with planned surgical resection or biopsy.
- •For Expansion phase:
- •Patients with mammographically detected breast nodules with planned surgical resection or biopsy.
- •For All phases:
- •ECOG 0 or 1
- •Estimated life expectancy > 3 months
- •Age ≥ 18 years
- •Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR <1.5, PTT <1.5X ULN
- •Adequate renal and hepatic function, with serum creatinine < 1.5 mg/dL, bilirubin < 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT and AST ≤ 2.5 x upper limit of normal or if liver metastases are present < 5 x upper limit of normal.
- •Female patients must be of non-child-bearing potential or use effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of study drug;
- •Ability to understand and provide signed informed consent that fulfills Institutional Review Board's guidelines.
- •Ability to return to Duke University Medical Center for adequate follow-up, as required by this protocol.
排除标准
- •Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
- •Medical or psychological impediment to probable compliance with the protocol.
- •Asthma under medical management
- •Uncontrolled high blood pressure
- •Presence of a known active acute or chronic infection including HIV or viral hepatitis (Hepatitis B and C)).
- •Pregnant or nursing women
研究组 & 干预措施
HS-196
HS-196 will be administered intravenously as a single dose
干预措施: HS-196 (Drug)
结局指标
主要结局
Fluorescence
时间窗: 1 day
Ratio of tumor to normal tissue fluorescence
次要结局
- Area Under the Curve AUC(1 week)
- Number of AEs(1 month)
- Radiant Efficiency(1 day)
- HS-196 Localization(1 day)
- Maximum Plasma concentration Cmax(1 week)
研究者
Herbert Lyerly
Professor
Duke University