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Alectinib Pharmacokinetic in Patients With ALK-rearranged NSCLC

Sponsor
Instituto Nacional de Cancerologia de Mexico (Other)
Overall Status
Recruiting
CT.gov ID
NCT05713006
Collaborator
(none)
45
Enrollment
1
Location
1
Arm
43
Anticipated Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Alectinib Oral Product
 Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Patients (≥18 years), both sex, clinical stage IIIB and IV, ALK-rearranged NSCLC treated by Thoracic Oncology Department at Instituto Nacional de Cancerología (INCan).Patients (≥18 years), both sex, clinical stage IIIB and IV, ALK-rearranged NSCLC treated by Thoracic Oncology Department at Instituto Nacional de Cancerología (INCan).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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.
Actual Study Start Date :
May 1, 2022
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alectinib escalation dose

Alecensa 150 mg Roche

Drug: 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.
Other Names:
  • Alecensa 150 mg Roche

    		•

    Outcome Measures

    Primary Outcome Measures

    1. AUC [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).

    2. Cmax [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).

    3. Cmin [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).

    4. Tmax [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)

    5. ORR [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

    6. Steady state [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.

    Secondary Outcome Measures

    1. Adverse events [From date of first dose administration through 9 weeks.]

      Tolerance during drug escalation doses (300, 450, and 600 mg) in the phase one portion based on the PK analysis.

    2. 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.]

      Adverse events under alectinib Administration a the chosen dose are measured in the phase two portion.

    3. 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.]

      Progression-free survival

    4. 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.]

      overall survival

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Thoracic Oncology Unit and Personalized Medicine Laboratory, Instituto Nacional de Cancerología Mexico City Mexico 14080

    Sponsors and Collaborators

    • Instituto Nacional de Cancerologia de Mexico

    Investigators

    • Principal Investigator: Oscar G Arrieta Rodriguez, M.D., M.Sc., Instituto Nacional de Cancerologia de Mexico

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Oscar Gerardo Arrieta Rodríguez, M.D., M.Sc., Instituto Nacional de Cancerologia de Mexico
    ClinicalTrials.gov Identifier:
    NCT05713006
    Other Study ID Numbers:
    • 022/023/ICI_CEI/1583/21_V.2
    First Posted:
    Feb 6, 2023
    Last Update Posted:
    Feb 6, 2023
    Last Verified:
    Jan 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Oscar Gerardo Arrieta Rodríguez, M.D., M.Sc., Instituto Nacional de Cancerologia de Mexico
    alectinib
    positive-ALK
    non small cell lung cancer
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung

    Study Results

    No Results Posted as of Feb 6, 2023