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ALK Inhibitor

Lorlatinib for Neuroblastoma

Phase 1
Waitlist Available
Research Sponsored by New Approaches to Neuroblastoma Therapy Consortium
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
All patients must have at least one of the following: Recurrent/progressive disease after the diagnosis of high-risk neuroblastoma, refractory disease, or persistent disease
Patients must have a life expectancy of at least 12 weeks and a Lansky (≤16 years) or Karnofsky (>16 years) score of at least 50
Must not have
Patients with an active or uncontrolled infection
Patient with current history of suicidal ideation and history of suicide attempt in their lifetime
Timeline
Screening 3 weeks
Treatment Varies
Follow Up all toxicities from enrollment until completion of course 2 (day 56)
Awards & highlights

Summary

This trial tests Lorlatinib, a new drug that blocks proteins helping cancer grow, in children whose neuroblastoma has returned or not responded to other treatments. The goal is to find the best dose and see how well it works.

Who is the study for?
This trial is for children and adults with high-risk neuroblastoma that's come back or hasn't responded to treatment. They must have certain types of tumor cells in their bone marrow, a life expectancy over 12 weeks, and good organ function. They can't have had lorlatinib before but other ALK inhibitors are okay. No recent cancer treatments or uncontrolled illnesses.
What is being tested?
The study tests Lorlatinib alone and with chemotherapy (Topotecan, Cyclophosphamide) in patients whose neuroblastoma has relapsed or is resistant to treatment. It starts by finding the safest dose of Lorlatinib (Phase 1), then expands to more patients once the right dose is found.
What are the potential side effects?
Possible side effects include reactions related to liver function changes, blood cell counts alterations leading to increased infection risk, potential kidney issues, heart problems like altered heart rhythm or function, as well as general symptoms such as fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My neuroblastoma has come back, is not responding, or hasn't gone away.
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I am expected to live at least 12 weeks and can do some daily activities on my own.
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I have been diagnosed with neuroblastoma confirmed by tests.
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My neuroblastoma is classified as high-risk.
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My neuroblastoma cancer has spread to my bone marrow.
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My tumor has an ALK mutation confirmed by a certified test.
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I have recovered from side effects of my previous cancer treatments.
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I have a lesion that tested positive for neuroblastoma or ganglioneuroblastoma.
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I have a tumor that can be measured.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have any ongoing or uncontrolled infections.
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I have thought about suicide recently and have attempted it before.
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I have chosen not to participate in the NANT 2004-05 study.
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I have had a stem cell transplant from a donor.
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My major organs are healthy enough to handle treatment.
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I have a history of HIV, hepatitis B, or hepatitis C.
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I am currently receiving hemodialysis.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~all toxicities from enrollment until completion of course 2 (day 56)
This trial's timeline: 3 weeks for screening, Varies for treatment, and all toxicities from enrollment until completion of course 2 (day 56) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Describe Hematological Toxicities (A1 and B1)
Describe Hematological Toxicities (A2)
Describe Hematological Toxicities (B2)
+6 more
Secondary study objectives
Overall Response A1 and B1
Overall Response A2
Overall Response B2
+3 more

Side effects data

From 2020 Phase 1 trial • 29 Patients • NCT03542305
13%
Diarrhoea
13%
Ecchymosis
13%
Dizziness
13%
Headache
13%
Upper respiratory tract infection
13%
Skin abrasion
100%
80%
60%
40%
20%
0%
Study treatment Arm
Moderate Impairment
Severe Impairment
Mild Impairment
Normal Function

Trial Design

4Treatment groups
Experimental Treatment
Group I: Cohort B2 (Combined w/ chemotherapy)Experimental Treatment4 Interventions
Lorlatinib will be given orally once daily continuously for 28 days, at the RP2D defined by cohort A1. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle.
Group II: Cohort B1 (Expansion)Experimental Treatment1 Intervention
Lorlatinib will be given orally once daily continuously for 28 days at the RP2D defined by cohort A1. This cohort will not begin enrollment until the recommended phase 2 dose is established from the dose escalation cohort A1.
Group III: Cohort A2 (Adult and large BSA)Experimental Treatment1 Intervention
Lorlatinib will be given at the adult recommended phase 2 dose (RP2D) of 100 mg orally once daily continuously for 28 days.
Group IV: Cohort A1 (Dose-finding)Experimental Treatment1 Intervention
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be assigned at the time of study registration. The starting dose for cohort A1 is 45 mg/m2/dose
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Topotecan
2017
Completed Phase 3
~2460
Lorlatinib
2018
Completed Phase 4
~460
Cyclophosphamide
2010
Completed Phase 4
~2320

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Neuroblastoma treatments often target specific genetic mutations and pathways involved in tumor growth. ALK inhibitors, such as Lorlatinib, work by blocking the activity of the anaplastic lymphoma kinase (ALK) gene, which can be mutated and drive cancer progression in some Neuroblastoma patients. By inhibiting ALK, these drugs can reduce tumor growth and spread. This targeted approach is crucial for Neuroblastoma patients as it offers a more personalized treatment option, potentially leading to better outcomes and fewer side effects compared to conventional chemotherapy.
Paediatric Strategy Forum for medicinal product development of multi-targeted kinase inhibitors in bone sarcomas: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.Pediatric drug development: a perspective from the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI).Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.

Find a Location

Who is running the clinical trial?

Ronan Thompson FoundationUNKNOWN
New Approaches to Neuroblastoma Therapy ConsortiumLead Sponsor
17 Previous Clinical Trials
1,631 Total Patients Enrolled
17 Trials studying Neuroblastoma
1,631 Patients Enrolled for Neuroblastoma
University of Southern CaliforniaOTHER
940 Previous Clinical Trials
1,614,482 Total Patients Enrolled
1 Trials studying Neuroblastoma
4 Patients Enrolled for Neuroblastoma

Media Library

Lorlatinib (ALK Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03107988 — Phase 1
Neuroblastoma Research Study Groups: Cohort B2 (Combined w/ chemotherapy), Cohort A2 (Adult and large BSA), Cohort A1 (Dose-finding), Cohort B1 (Expansion)
Neuroblastoma Clinical Trial 2023: Lorlatinib Highlights & Side Effects. Trial Name: NCT03107988 — Phase 1
Lorlatinib (ALK Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03107988 — Phase 1
~1 spots leftby Dec 2024