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.
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.
• Both sexes
• ≥ 18 years old
• Pathologically confirmed diagnosis of NSCLC
• Stage IIIB - IV by the American Joint Committee of Cancer Version 8.
• 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