Alectinib Pharmacokinetic in Patients With NSCLC

NCT ID: NCT05713006

Last Updated: 2025-05-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-01

Study Completion Date

2025-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-small Cell Lung Cancer Stage IIIB ALK Gene Mutation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Patients (≥18 years), both sex, clinical stage IIIB and IV, ALK-rearranged NSCLC treated by Thoracic Oncology Department at Instituto Nacional de Cancerología (INCan).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Alectinib escalation dose

Alecensa 150 mg Roche

Group Type EXPERIMENTAL

Alectinib Oral Product

Intervention Type DRUG

Alectinib 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.

Interventions

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Alectinib Oral Product

Alectinib 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.

Intervention Type DRUG

Other Intervention Names

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Alecensa 150 mg Roche

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto Nacional de Cancerologia de Mexico

OTHER

Sponsor Role lead

Responsible Party

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Oscar Gerardo Arrieta Rodríguez

Head of the Thoracic Oncology Unit and Personalized Medicine Laboratory

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Oscar G Arrieta Rodriguez, M.D., M.Sc.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Cancerologia de Mexico

Locations

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Thoracic Oncology Unit and Personalized Medicine Laboratory, Instituto Nacional de Cancerología

Mexico City, , Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Oscar G Arrieta Rodriguez, M.D., M.Sc.

Role: CONTACT

5556280400 ext. 71101

Facility Contacts

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Oscar G Arrieta, M.D., M.Sc.

Role: primary

5556280400 ext. 71101

References

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Morcos PN, Nueesch E, Jaminion F, Guerini E, Hsu JC, Bordogna W, Balas B, Mercier F. Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 2018 Jul;82(1):129-138. doi: 10.1007/s00280-018-3597-5. Epub 2018 May 10.

Reference Type BACKGROUND
PMID: 29748847 (View on PubMed)

Sivignon M, Monnier R, Tehard B, Roze S. Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France. PLoS One. 2020 Jan 16;15(1):e0226196. doi: 10.1371/journal.pone.0226196. eCollection 2020.

Reference Type BACKGROUND
PMID: 31945065 (View on PubMed)

Carlson JJ, Suh K, Orfanos P, Wong W. Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer. Pharmacoeconomics. 2018 Apr;36(4):495-504. doi: 10.1007/s40273-018-0625-6.

Reference Type BACKGROUND
PMID: 29488070 (View on PubMed)

Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. doi: 10.1016/S0140-6736(17)30565-2. Epub 2017 May 10.

Reference Type BACKGROUND
PMID: 28501140 (View on PubMed)

Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.

Reference Type BACKGROUND
PMID: 28586279 (View on PubMed)

Other Identifiers

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022/023/ICI_CEI/1583/21_V.2

Identifier Type: -

Identifier Source: org_study_id

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