Lorlatinib for Brain Tumors

Recruiting at 16 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

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.

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.

How is the drug Lorlatinib unique for treating brain tumors?

Lorlatinib is unique because it is a third-generation drug that can effectively penetrate the blood-brain barrier (a protective layer around the brain) and target specific mutations in cancer cells, making it particularly effective for brain tumors that have spread from other areas, like lung cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Lorlatinib for brain tumors?

Lorlatinib has shown effectiveness in treating brain metastases (spread of cancer to the brain) in patients with certain types of lung cancer, as it can penetrate the blood-brain barrier (a protective layer around the brain) and target cancer cells there. ^{1 2 3 5 6}

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. United States pubmed.ncbi.nlm.nih.gov

A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib. [2022]

2. Switzerland 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of lorlatinib treatment in ALK rearrangement lung cancer with severe symptomatic central nervous system metastases and poor performance status. [2021]

5. Spain pubmed.ncbi.nlm.nih.gov

Lorlatinib for the treatment of patients with non-small cell lung cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The underlying mechanisms of lorlatinib penetration across the blood-brain barrier and the distribution characteristics of lorlatinib in the brain. [2021]