Lorlatinib for Brain Tumors
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to evaluate the effectiveness and safety of the drug lorlatinib in treating children with high-grade glioma, particularly those with specific changes in the ALK or ROS1 genes. The study will test lorlatinib alone and in combination with various chemotherapy treatments to assess its efficacy following initial treatments like radiation therapy. Children newly diagnosed with high-grade glioma, especially if their cancer cells exhibit certain genetic changes (fusions in ALK or ROS1), may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how lorlatinib works in children, providing an opportunity to be among the first to receive this treatment.
Will I have to stop taking my current medications?
The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers before starting lorlatinib. Also, avoid using lorlatinib with certain CYP3A substrates and P-glycoprotein substrates like digoxin.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that lorlatinib is generally safe for patients with ALK-positive non-small cell lung cancer (NSCLC), even if the cancer has spread to the brain. Studies have found that it can help shrink tumors in these patients. Some side effects, such as high cholesterol and swelling, have been reported, but proper medical care can usually manage them.
Although limited data exists on using lorlatinib for brain tumors in children, its approval for treating NSCLC suggests reasonable safety. Since this trial is in the early stages, it primarily focuses on assessing the drug's safety, which is important to consider when deciding whether to participate.12345Why are researchers excited about this trial's treatments?
Researchers are excited about Lorlatinib for treating brain tumors because it offers a unique approach compared to traditional treatments like surgery, radiation therapy, and chemotherapy. Lorlatinib is designed to specifically target and inhibit a protein called ALK, which plays a role in the growth of certain tumors. This targeted action could potentially lead to more effective outcomes with fewer side effects. Additionally, Lorlatinib's ability to penetrate the blood-brain barrier makes it promising for treating brain tumors, a significant challenge for many existing drugs. These features make Lorlatinib a potentially groundbreaking option for patients with brain tumors.
What evidence suggests that this trial's treatments could be effective for high-grade glioma?
Research has shown that lorlatinib yields promising results for treating cancers with ALK or ROS1 gene changes. Studies found that 76% of patients experienced tumor shrinkage or disappearance with lorlatinib. It also extended the time patients lived without cancer progression. In some cases, up to 60% of patients survived without cancer progression after five years. Lorlatinib proved effective against brain tumors, which is crucial for treating brain cancers. This trial will explore various treatment arms, including Lorlatinib Monotherapy, Lorlatinib Maintenance Therapy post-RT, and combinations with BABY POG and HIT-SKK chemotherapy. These findings suggest that lorlatinib could be effective for high-grade gliomas with ALK or ROS1 changes.678910
Who Is on the Research Team?
Maryam Fouladi, MD
Principal Investigator
Nationwide Children's Hospital
Hamza Gorsi, MD
Principal Investigator
Children's Hospital of Michigan
Susan Chi, MD
Principal Investigator
Dana-Farber Cancer Institute
Are You a Good Fit for This Trial?
This trial is for children newly diagnosed with high-grade gliomas, a type of brain tumor, that have specific genetic changes called ALK or ROS1 fusion. The exact eligibility criteria are not provided but typically include factors like age, health status, and the specifics of their cancer diagnosis.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive lorlatinib monotherapy for two 28-day cycles, followed by evaluation and potential continuation with chemotherapy or radiation therapy based on response
Maintenance Therapy
Participants continue with lorlatinib monotherapy or in combination with chemotherapy or post-radiation therapy, depending on age and response
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Lorlatinib
Trial Overview
The study is testing lorlatinib's effectiveness on these brain tumors when given alone, alongside two different chemotherapy regimens (chemotherapy 1 and chemotherapy 2), or after radiation therapy. It aims to find out how well it works and its safety in these various combinations.
How Is the Trial Designed?
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Treatment groups
Experimental Treatment
Lorlatinib administered as monotherapy by PO (per os) or NG (nasogastric) for two 28-day cycles at 115 mg/m2/day (or maximum 200mg/dose), after which disease evaluation by Magnetic Resonance Imaging (MRI) imaging will be performed.
Lorlatinib monotherapy x2 cycles followed by Radiation Therapy and continue lorlatnib maintenance monotherapy (115 mg/m2/day) 28 days post completion of RT for 12 cycles
Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and HIT-SKK chemotherapy backbone (cyclophosphamide, vincristine, methotrexate, carboplatin, etposide) The recommended HIT-SKK chemotherapy backbone regimen consists of modular chemotherapy cycles, three courses of 4 blocks each (Element IIS, Element IIIS/1, Element IIIS/2, and Element IVS). Each element will be administered consecutively at 2-3-week intervals. Elements IIS and IVS cycles will be repeated twice thereafter. The entire length of treatment for HIT-SKK will be approximately 42 weeks.
Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and BABY-POG chemotherapy backbone (vincristine, cyclophosphamide, cisplatin) The BABYPOG chemotherapy backbone regimen will consist of six 12-week courses. Each course will consist of cycles A, A2 and B, which will be administered consecutively, in 28-day cycles for a total of 72 weeks
Lorlatinib is already approved in United States, European Union, Japan, Canada for the following indications:
- Metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement
- Advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement
- Unresectable, advanced/recurrent non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement
- Metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement
Find a Clinic Near You
Who Is Running the Clinical Trial?
Nationwide Children's Hospital
Lead Sponsor
Pfizer
Industry Sponsor
Albert Bourla
Pfizer
Chief Executive Officer since 2019
PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki
Patrizia Cavazzoni
Pfizer
Chief Medical Officer
MD from McGill University
Published Research Related to This Trial
Citations
Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety ...
Lorlatinib significantly improved progression-free survival (PFS) versus crizotinib and showed robust intracranial activity in patients with previously ...
2.
cancer.gov
cancer.gov/news-events/cancer-currents-blog/2024/lorlatinib-alk-positive-lung-cancer-initial-treatmentLorlatinib Slows Growth of ALK-Positive Lung Cancers ...
After 5 years of follow-up data, the investigators found, 60% of the participants in the lorlatinib group were alive without the disease having ...
3.
pfizer.com
pfizer.com/news/press-release/press-release-detail/pfizers-lorbrenar-crown-study-shows-majority-patients-alkPfizer's LORBRENA® CROWN Study Shows Majority ...
60% of patients treated with LORBRENA (95% CI, 51-68) were alive without disease progression after five years compared to 8% (3-14) on the XALKORI treatment ...
Clinical Trial Results | Lorbrena® (lorlatinib) | Safety Info
76% of patients had their tumors shrink or disappear while taking LORBRENA. In a complete response, all signs of cancer disappear.
Real-world analysis of the efficacy and safety of lorlatinib in ...
Among the 23 patients without brain metastases before lorlatinib treatment, 3 patients (13.0%) got CR, 8 patients (34.8%) got PR, and 12 ...
Lorbrena® (lorlatinib) Patient Site | Safety Info
LORBRENA was specifically designed to cross the blood-brain barrier and has been shown to help shrink ALK+ NSCLC tumors that have spread to the brain. Section ...
LORBRENA® (lorlatinib) First Line Efficacy | Safety Info
Find efficacy information for a first line study of LORBRENA® in patients with ALK+ metastatic non-small cell lung cancer (NSCLC). See risks and benefits.
Updated Efficacy and Safety of Lorlatinib in a Phase 2 ...
These results support using lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases.
Brief Report Long-Term Efficacy and Safety of Lorlatinib in ...
At the data cutoff of September 20, 2021, median progression-free survival was not reached with lorlatinib and 11.1 months with crizotinib (hazard ratio = 0.36) ...
Final Overall Survival and Long-Term Safety of Lorlatinib in ...
We present the overall survival (OS) and long-term safety of lorlatinib in patients with advanced ALK-positive NSCLC from the final analyses of the pivotal ...
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