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.

Plain English Summary

Alectinib Pharmacokinetic in Patients With NSCLC is a Phase 2 clinical trial sponsored by Instituto Nacional de Cancerologia de Mexico studying Non-small Cell Lung Cancer Stage IIIB, ALK Gene Mutation. This trial is for patients with a specific type of advanced non-small cell lung cancer (NSCLC) that has an ALK gene rearrangement. It tests how the drug alectinib is absorbed and processed by the body (pharmacokinetics) when given at different doses. Participants will receive alectinib, and their response to the treatment will be monitored. There are no alternative treatments offered within this trial; standard care outside the trial is the alternative. The trial aims to enroll 45 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18 and older with a confirmed diagnosis of advanced NSCLC (Stage IIIB-IV) and an ALK gene rearrangement. Must have previously been treated with an ALK inhibitor and one line of chemotherapy. Patients must have a good performance status (Karnofsky score of 70% or higher) and adequate organ function. Cannot have carcinomatous meningitis, active hepatitis, or HIV infection, and must not be pregnant or breastfeeding. This trial is studying Non-small Cell Lung Cancer Stage IIIB, ALK Gene Mutation, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how much of the drug is in the blood at different times, helping doctors understand the best dose to use for maximum benefit and minimal side effects. The specific primary outcome measures are: AUC (Amount of drug concentration between 0 to 12 hours after first drug administration); 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); 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); Tmax (From first dose administration through the following 12 hours (day 1)); ORR (From first dose administration up to disease progression by CT scan every 6 weeks, through study completion.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it aims to better understand how alectinib is processed in the body at different doses, which can help optimize its use for patients with ALK-rearranged lung cancer who Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer Stage IIIB, ALK Gene Mutation, where improved treatment options are needed.

Investor Insight

This trial focuses on a specific subset of lung cancer patients, indicating a targeted therapy approach. Success could refine dosing for alectinib, a known treatment in this area, potentially strength Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, especially regarding your specific cancer type and previous treatments. Participation involves taking alectinib orally twice a day, with regular blood draws to monitor drug levels and potential side effects. You will continue treatment until your cancer progresses, you experience unacceptable side effects, or you decide to stop. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 45 participants

Interventions

• 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.

Primary Outcomes

• AUC (Amount of drug concentration between 0 to 12 hours after first drug administration)
• 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)
• 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)
• Tmax (From first dose administration through the following 12 hours (day 1))
• ORR (From first dose administration up to disease progression by CT scan every 6 weeks, through study completion.)

Secondary Outcomes

• 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.)

Full Eligibility Criteria

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.

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• ALK-positive Lung Cancer
• Lung Adenocarcinoma
• Metastatic Lung Cancer
• Targeted Cancer Therapy
• Tyrosine Kinase Inhibitors
• Oncology
• Thoracic Oncology
• Cancer Genomics
• Personalized Medicine

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