A Phase 1 Dose Escalation of ArtemiCoffee in Patients With Advanced Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Recommended Phase II Dose
研究概览
简要总结
This is a phase I dose-escalation study of Artemisia annua (Aa) in patients with advanced ovarian cancer who have completed front-line chemotherapy with carboplatin and paclitaxel. The primary objective of this study is to determine the recommended phase II dose (RP2D) of Artemisia annua.
详细描述
This is a phase I dose-escalation study of Artemisia annua (Aa) decaffeinated coffee in patients with advanced ovarian cancer who have completed front-line chemotherapy with carboplatin and paclitaxel. The primary objective of this study is to determine the recommended phase II dose (RP2D) of Aa decaf coffee pods. Sequential cohorts of three patients per cohort will have escalating doses of Aa, starting with one cup per day (450mg) and with a maximum of 4 cups per day (1800mg). After identifying the RP2D, the study will evaluate an expansion cohort of 6 patients for further tolerability and secondary endpoints. The secondary endpoints include: 1) Efficacy as measured by time to tumor progression or recurrence; 2) the ability of Aa decaf coffee to influence downstream biomarkers of the NRF2/KEAP1 signaling pathway; and 3) plasma concentrations of artemisinin and dihydroartemisinin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- 是
入选标准
- •Able to understand and willing to sign a written informed consent document.
- •Age ≥ 18 years.
- •Patients diagnosed with Stage II-IV ovarian cancer who have completed initial first-line therapy with carboplatin and paclitaxel and achieved a complete response.
- •Creatinine clearance ≥ 60 mL/min
- •Total bilirubin ≤ 1.5 x ULN, and AST and ALT ≤ 3.0 x ULN
- •GOG Performance Status ≤ 2.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study visits, in the opinion of the treating physician.
- •Pregnant women are excluded from this study.
- •Concurrent use of strong inducers of CYP2A6, including phenobarbital and rifampin
- •Women with active gastric ulcers are excluded from this study.
- •Patients who are receiving concurrent maintenance therapy with a PARP inhibitor for a known hereditary recombinant deficiency (HRD) mutation. Bevacizumab maintenance therapy is allowed.
- •Concurrent use of nevirapine, ritonavir and strong UGT inhibitors or inducers.
研究组 & 干预措施
Dose 1 - 450mg Artemisia annua
Participants in this group will consume 1 cup of decaffeinated coffee (450 mg Artemisia annua).
干预措施: Artemisia annua 450mg (Drug)
Dose 2 - 900mg Artemisia annua
Participants in this group will consume 2 cups of decaffeinated coffee (900 mg Artemisia annua).
干预措施: Artemisia annua 900mg (Drug)
Dose 3 - 1350mg Artemisia annua
Participants in this group will consume 3 cups of decaffeinated coffee (1350 mg Artemisia annua).
干预措施: Artemisia annua 1350mg (Drug)
Dose 5 - 1800mg Artemisia annua
Participants in this group will consume 4 cups of decaffeinated coffee (1800 mg Artemisia annua).
干预措施: Artemisia annua 1800mg (Drug)
Dose Expansion - Recommended Phase II Dose
This cohort will be an expansion of 6 patients for further tolerability and secondary endpoints analysis. They will consume the recommended phase II dose (dependent on prior analysis).
干预措施: Artemisia annua - recommended phase II dose (Drug)
结局指标
主要结局
Recommended Phase II Dose
时间窗: 150 days
This study will determine the recommended phase II dose of Artemisia annua decaffeinated coffee. Once the dose escalation is finished or 12 patients are evaluated for the dose-limiting toxicity (DLT), the final recommended phase II dose will be determined by isotonic regression to pool the DLT information across all dose levels.
次要结局
- Progression Free Survival(150 days)
研究者
Frederick R. Ueland, M.D.
Professor
University of Kentucky