Lorlatinib for Brain Tumors

Not currently recruiting at 18 trial locations

Overseen By Kelsey H Troyer, PhD

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nationwide Children's Hospital

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: Pregnancy, Organ transplant, Psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

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. ^{1 2 3 4 5}

Why 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. ^{6 7 8 9 10}

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

All patients and/or their parents or legally authorized representatives must sign a written informed consent

I am 21 years old or younger.

My brain tumor is a high-grade type like glioblastoma.

Exclusion Criteria

Pregnant or breast-feeding women

Patients who have received prior solid organ transplantation

I have a condition that affects how my body absorbs medication taken by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lorlatinib monotherapy for two 28-day cycles, followed by evaluation and potential continuation with chemotherapy or radiation therapy based on response

8 weeks

Maintenance Therapy

Participants continue with lorlatinib monotherapy or in combination with chemotherapy or post-radiation therapy, depending on age and response

12-26 cycles of 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days following end of protocol 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?

Group I: Lorlatinib Monotherapy Experimental Treatment 1 Intervention

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.

Group II: Lorlatinib Maintenance Therapy post RT Experimental Treatment 2 Interventions

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

Group III: Lorlatinib Combination with HIT-SKK chemotherapy Experimental Treatment 2 Interventions

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.

Group IV: Lorlatinib Combination with BABY POG chemotherapy Experimental Treatment 2 Interventions

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:

Approved in United States as Lorbrena for:

• Metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement

Approved in European Union as Lorbrena for:

• Advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement

Approved in Japan as Lorbrena for:

• Unresectable, advanced/recurrent non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement

Approved in Canada as Lorbrena for:

• Metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

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

Lorlatinib shows significant brain penetration and demonstrates autoinduction after multiple doses, which means its clearance increases with continued use, potentially affecting dosing strategies.

In a study involving 329 patients (54 in phase I and 275 in phase II), lorlatinib's plasma exposure increased proportionally with single doses and slightly less so with multiple doses, indicating consistent efficacy in treating ALK-positive non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Lorlatinib After Single and Multiple Dosing in Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: Results from a Global Phase I/II Study. Chen, J., O'Gorman, MT., James, LP., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9622589/

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-treatment

Lorlatinib 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-alk

Pfizer'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 ...

4. lorbrena.com lorbrena.com/clinical-study-results

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.

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1577607/full

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 ...

6. lorbrena.com lorbrena.com/what-is-lorbrena

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 ...

7. lorbrena.pfizerpro.com lorbrena.pfizerpro.com/first-line-efficacy

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.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38879393/

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.

9. sciencedirect.com sciencedirect.com/science/article/pii/S266636432400002X

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) ...

10. jto.org jto.org/article/S1556-0864(24)02484-5/fulltext

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 ...