A Phase I/II Open-label Clinical Trial to Evaluate the Pharmacokinetics of Alectinib With Sequential Dose Escalation in Patients Diagnosed With ALK-rearranged Advanced Non-small Cell Lung Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Tmax
研究概览
简要总结
This interventional study aims to determine the pharmacokinetics of orally administered alectinib with dose escalation from 300 mg to 600 mg twice daily in Mexican patients with advanced ALK-positive NSCLC.
The main question it aims to answer is: what will be the peak plasma concentrations of alectinib following sequential dose escalation (300, 450, and 600 mg BID) over nine weeks of pharmacokinetic evaluation (phase I) in Mexican patients with advanced ALK-rearranged NSCLC?
In phase I (on days 0, 21, and 42), oral alectinib will be administered twice per day (BID) to patients with ALK-positive NSCLC; starting with 300 mg BID in 21-day cycles and dose escalation in 150 mg increments until 600 mg BID. Blood samples will be taken before and after administration of each dose (on days 1, 22, and 43). The primary endopoints in phase I will be dose-limiting toxicity (DLT) and PK parameters (Cmax. maximum plasma concentration; Tmax: time to reach maximum concentration: AUC 1-12: area under plasma ocncentrations-time curve steady-state concentration). At the end of the last blood collection (at day 43), the evaluation of each cycle will be at 600 mg, and the participant will be discharged to continue their treatment on an outpatient basis. Phase one will finish on day 63 of the study.
In phase II, the chosen BID dose based on the phase I portion will be administrated until disease progression, development of unacceptable side effects, or withdrawal of consent. The primary endpoint in phase 2 is the overall response rate (ORR) per RECIST V.1.1.
详细描述
Alectinib will be administrated under fast conditions.
The primary endpoint of the phase II part was ORR. Other secondary endpoints in phase II are progression-free survival (PFS), overall survival (OS), intracranial response (ICR), and duration of response (DOR).
Exploratory endpoints in this follow-up analysis included the evaluation of the correlation between tumor shrinkage and PFS and chosen dose to relieve cancer symptoms.
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
- •Both sexes
- •≥ 18 years old
- •Pathologically confirmed diagnosis of NSCLC
- •Stage IIIB - IV by the American Joint Committee of Cancer Version
- •Recurrent disease (at least 180 days from curative intent treatment)
- •ALK rearrangements tested by FDA-approved tests (IHQ or FISH)
- •Karnofsky PS scale ≥ 70%
- •Having received first-line treatment with anti-ALK inhibitors and one previous line of platinum-based chemotherapy.
- •Measurable disease as referred by RECIST version 1.1
- •Symptomatic brain metastases could receive prior treatment with radiotherapy or surgery for at least two weeks before treatment initiation.
- •Asymptomatic brain metastases could not receive local therapy before study inclusion.
- •Negative highly sensitive pregnancy test (serum or urine) within 72 days before first dose intervention.
- •Sexually active patients should use a contraceptive method with a failure rate of less than 1% per year.
- •Signed written informed consent
- •Adequate organ function (hematological, liver, and renal function)
- •Life expectancy of at least 12 weeks
排除标准
- •Carcinomatous meningitis confirmed by a positive CRL cytology or highly suspicious brain MRI.
- •Previous malignancies except for any carcinoma in-situ
- •Treatment with other anti-cancer therapy
- •Participating in other clinical trials in the former four weeks
- •Any other serious condition or uncontrolled active infection, altered mental status, or psychiatric condition that, in the investigator´s opinion, would limit the ability of an individual to meet the requirements of the study or which affects the interpretability of the results.
- •Active hepatitis virus infection (any serotype) or chronic infection with a potential risk of reactivation evaluated through a serological panel.
- •Active HIV infection.
- •Breastfeeding.
研究组 & 干预措施
Alectinib escalation dose
Alecensa 150 mg Roche
干预措施: Alectinib Oral Product (Drug)
结局指标
主要结局
Tmax
时间窗: From first dose administration through the following 12 hours (day 1)
Time in witch Cmax is reached in each dose of the drug (300,450 and 600 mg)
AUC
时间窗: Amount of drug concentration between 0 to 12 hours after first drug administration
The area under the curve (AUC). Pharmacokinetic behavior of the initial alectinib for each given dose (300, 450 and 600 mg).
Cmax
时间窗: From baseline control pre-dose, 0.50, 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00 and 11.90 hours
Highest concentration of drug in blood (Serum) for each given dose (300, 450 and 600 mg).
Cmin
时间窗: From baseline control pre-dose, 0.50, 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00 and 11.90 hours
Lowest concentration of drug in blood (Serum) for each given dose (300, 450 and 600 mg).
ORR
时间窗: From first dose administration up to disease progression by CT scan every 6 weeks, through study completion.
overall response rate is measured in phase two
Steady state
时间窗: For phase two: between 2 and 4 months of treatment with investigators chosen dose.
The amount of drug in the plasma has built up to a therapeutically effective concentration level, and as long as regular doses are administered to balance the amount of drug being cleared, the drug will continue to be active.
次要结局
- Adverse events(From date of first dose administration through 9 weeks.)
- Drug toxicity(From date of starting phase 2 portion until the date of first documented progression date or death from any cause, whichever comes first, assessed up to 60 months.)
- PFS(From date of first dose administration until the date of first documented progression date or death from any cause, whichever comes first, assessed up to 100 months.)
- OS(From date of first dose administration until the date of documented death from any cause or last follow-up, whichever comes first, assessed up to 120 months.)
研究者
Oscar Gerardo Arrieta Rodríguez
Head of the Thoracic Oncology Unit and Personalized Medicine Laboratory
Instituto Nacional de Cancerologia de Mexico