Alectinib Pharmacokinetic in Patients With NSCLC
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstituto Nacional de Cancerologia de Mexico
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Both sexes
≥ 18 years old
Pathologically confirmed diagnosis of NSCLC
Stage IIIB - IV by the American Joint Committee of Cancer Version 8.
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Alectinib Oral Product
DrugAlectinib is administered with a sequential dose escalation every 21 days from 300 to 600mg twice daily in the phase 1 portion. In phase 2, patients received an investigator-chosen dose based on the PK analysis.
Treatment groups
45 Participants
are divided into 1 treatment groupGroup A: Alectinib escalation doseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
AUC
The area under the curve (AUC). Pharmacokinetic behavior of the initial alectinib for each given dose (300, 450 and 600 mg).
Time frame
Amount of drug concentration between 0 to 12 hours after first drug administration2
Cmax
Highest concentration of drug in blood (Serum) for each given dose (300, 450 and 600 mg).
Time frame
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 hours3
Cmin
Lowest concentration of drug in blood (Serum) for each given dose (300, 450 and 600 mg).
Time frame
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 hours4
Tmax
Time in witch Cmax is reached in each dose of the drug (300,450 and 600 mg)
Time frame
From first dose administration through the following 12 hours (day 1)Secondary outcomes
1
Adverse events
Tolerance during drug escalation doses (300, 450, and 600 mg) in the phase one portion based on the PK analysis.
Time frame
From date of first dose administration through 9 weeks.2
Drug toxicity
Adverse events under alectinib Administration a the chosen dose are measured in the phase two portion.
Time frame
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.3
PFS
Progression-free survival
Time frame
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.4
OS
overall survival
Time frame
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.Sponsors and contacts
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Source ClinicalTrials.gov