Actively Recruiting
Lorlatinib Plus Local Consolidation Therapy in ALK-Positive Advanced Non-Small Cell Lung Cancer
Led by M.D. Anderson Cancer Center · Updated on 2026-05-05
30
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating treatments for patients with advanced non-small cell lung cancer (NSCLC) that has a specific genetic change called ALK rearrangement. This phase 2 trial focuses on patients who have not previously received tyrosine kinase inhibitors (TKIs) and aims to compare the time patients live without cancer progression when treated with lorlatinib alone versus lorlatinib combined with local consolidation therapy (LCT). The study also seeks to assess safety, overall survival, and molecular markers related to treatment resistance. Participants initially receive lorlatinib, an oral medication, daily for 12 weeks before randomization. Some patients who have been on other first-line ALK TKIs for up to 4 weeks and switched to lorlatinib will also complete a total of 12 weeks on lorlatinib prior to randomization. The trial has two experimental groups: one receiving lorlatinib alone, and the other receiving lorlatinib plus local consolidation therapy. The study includes biomarker evaluations using blood and tissue samples collected before and after LCT. During the trial, participants undergo various assessments including safety monitoring for adverse events over about one year. Researchers will collect blood samples to study circulating tumor DNA and perform biopsies after disease progression to understand resistance mechanisms. Participants must provide informed consent and comply with study procedures, with ongoing evaluations of organ function, heart health, and pregnancy status as part of eligibility and safety monitoring. The total study duration and follow-up depend on individual participant progress.
CONDITIONS
Brief Title
Lorlatinib Plus Local Consolidation Therapy In ALK Positive Advanced Non-Small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed diagnosis of stage IV NSCLC or recurrent NSCLC not suitable for definitive multimodality therapy
- Documented ALK rearrangement detected by FISH, IHC, tissue NGS, or cfDNA NGS
- Tyrosine kinase inhibitor (TKI) naive, or after/during up to 12 weeks of first-line lorlatinib treatment without disease progression, or after/during up to 4 weeks of first-line alectinib, brigatinib, or ensartinib without disease progression and switched to lorlatinib
- Candidate for local consolidation therapy as determined by the treating physician
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Male or female aged 18 years or older
- Adequate organ function based on specific laboratory values
- Female patients of childbearing potential must have a negative pregnancy test at screening
- Women of childbearing potential must use highly effective contraception or abstain from heterosexual intercourse during the study and for 4 months after last dose
- Male patients must agree to use effective barrier contraception or abstain from heterosexual intercourse during the study and for 4 months after last dose
- Normal QT interval on screening ECG (QTcF ≤450 ms in males, ≤470 ms in females)
- Willingness and ability to provide informed consent and comply with study protocol
You will not qualify if you...
- Diagnosis of another primary malignancy except certain treated cancers or those with at least 2 years since completion of radical treatment
- Prior treatment with any ALK-targeted TKI except allowed limited use as per inclusion criteria
- More than one cycle of chemotherapy or immunotherapy for advanced disease
- Symptomatic central nervous system metastases or asymptomatic CNS disease requiring increasing corticosteroids within 7 days before enrollment
- Current spinal cord compression
- Pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening
- Known or suspected allergy to lorlatinib or its excipients
- Gastrointestinal conditions affecting oral drug absorption
- Uncontrolled hypertension
- Radiation therapy within 14 days before randomization except stereotactic radiosurgery or body radiation
- Major surgery within 30 days before enrollment
- Significant uncontrolled cardiovascular disease or recent myocardial infarction, unstable angina, or heart failure
- Cerebrovascular accident within 6 months before first study dose
- Ongoing active infection requiring intravenous antibiotics
- Use of other anti-cancer agents during the study
- History of allergic reactions to similar compounds
- Known HIV infection
- Pregnancy or breastfeeding
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 12 weeks induction period prior to randomization
Participants receive lorlatinib orally daily during an induction period of 12 weeks prior to randomization. Participants may also receive local consolidation therapy (LCT) depending on their treatment group assignment.
Visits as per treatment protocol during induction and LCT
Duration - Up to 1 year or until study completion
Participants are monitored for safety, adverse events, and overall survival after treatment.
Regular follow-up visits during study period
Trial Site Locations
Total: 1 location
1
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
Y
Yasir Y Elamin, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here