A Phase I/II Trial of Short Course Pre-Operative Ritonavir To Determine Akt Inhibition in Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Inhibition of breast cancer by targeting Hsp90-Akt pathway
研究概览
简要总结
RATIONALE: Ritonavir may stop the growth of tumor cells by blocking some of the enzymes needed for cancer cell growth. Studying samples of blood and tissue from patients with breast cancer in the laboratory may help doctors learn more about the effects of ritonavir on biomarkers involved in breast cancer growth.
PURPOSE: This phase I/II trial is studying the best dose of ritonavir and its effects on biomarkers in women undergoing surgery for newly diagnosed breast cancer.
详细描述
OBJECTIVES:
- Determine the effects of ritonavir on Akt activity, UPR, Ki67 LI, and ROS in a triple-negative breast cancer model.
- Determine the maximum tolerated dose of ritonavir in women with newly diagnosed breast cancer. (Phase I - enrollment complete)
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study. *Note: This trial never moved forward to Phase ll.
Control Group - Five patients with estrogen receptor positive (ER+) and human epidermal growth factor 2 negative (HER2-) breast cancer are enrolled before the start of phase I recruitment.
Phase I Group - Twelve breast cancer patients with either 1)ER+, HER2-, or 2)ER+, HER2+, or 3) ER-, HER2+, or 4) ER-, PR+, HER2-, or 5) ER-, PR-, HER2- will be enrolled for dose escalation study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ritonavir - Escalating Doses (I)
Standard phase I dose escalation (with therapeutic conventional surgery) will be used with 3 levels of ritonavir given - 200 mg bid, 400 mg bid, and 600 mg bid for the following groups:
- ER+, HER2-
- ER+, HER2+
- ER-, HER2+
- ER-, PR+, HER2-
- ER-, PR-, HER2-
干预措施: therapeutic conventional surgery (Procedure)
Control Arm - No Ritonavir
Five ER+, HER2- breast cancer patients meeting all study eligibility will be enrolled prior to the start of phase I recruitment to act as controls (no ritonavir will be given-will receive therapeutic conventional surgery) to confirm that anesthesia does not affect EET levels. Core biopsies, surgical tumor/normal tissue and pre- and post- surgery blood samples will be collected for comparison with the treatment group.
干预措施: therapeutic conventional surgery (Procedure)
Ritonavir - Escalating Doses (I)
Standard phase I dose escalation (with therapeutic conventional surgery) will be used with 3 levels of ritonavir given - 200 mg bid, 400 mg bid, and 600 mg bid for the following groups:
- ER+, HER2-
- ER+, HER2+
- ER-, HER2+
- ER-, PR+, HER2-
- ER-, PR-, HER2-
干预措施: ritonavir (Drug)
Ritonavir - Maximum Tolerated Dose (II)
Phase II: Once the maximum tolerated dose (MTD) of ritonavir is established, 19 ER+, HER2- patients will be enrolled at MTD during the phase II component along with therapeutic conventional surgery.
干预措施: ritonavir (Drug)
Ritonavir - Maximum Tolerated Dose (II)
Phase II: Once the maximum tolerated dose (MTD) of ritonavir is established, 19 ER+, HER2- patients will be enrolled at MTD during the phase II component along with therapeutic conventional surgery.
干预措施: therapeutic conventional surgery (Procedure)
结局指标
主要结局
Inhibition of breast cancer by targeting Hsp90-Akt pathway
时间窗: Pre and Post Treatment
次要结局
- Activation of apoptosis markers(Pre and Post Treatment)
- Modulation of autophagy markers(Pre and Post Treatment)
- Alteration of plasma levels of eicosanoids(Pre Treatment and 3 Hours Post Treatment)
- Induction of Hsp70 in peripheral blood mononuclear cells(Pre Treatment and 3 Hours Post Treatment)
- Reduction of ERα in ERα+ tumors(Pre and Post Treatment)
- Changes in TNF-α and IL-6 levels as well as reduction in intratumoral nuclear NF-kB and phospho-Stat3(Pre and Post Treatment)
- Alteration of urine eicosanoid levels(Pre and Post Treatment)
- Alteration of plasma and urine eicosanoid levels resulting from tumor resection.(Pre and Post Treatment)
- Induction of the unfolded protein response (UPR) assayed by grp78 or related markers (phospho-PERK, ATF-4, and CHOP)(pre- and post-surgery)
- inhibition of tumor growth markers (Ki67 LI, Hsp90, phosphorylated AKT)(pre- and post-surgery)