Real World Data Collection Pediatric Neuroblastoma Treated With Lorlatinib

REAL WORLD DATA COLLECTION AMONG PEDIATRIC NEUROBLASTOMA PATIENTS TREATED WITH LORLATINIB THROUGH EXPANDED ACCESS PROGRAM

The overall goal of this real-world data collection is to assess demographic, clinical characteristics and real-world effectiveness of pediatric neuroblastoma patients treated with lorlatinib through the expanded access program.

Study Overview

• Status: Terminated
• Conditions: Neuroblastoma
• Intervention / Treatment: Drug: lorlatinib

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Australia
  • Camperdown, New South Wales, 2050 Australia, Australia
    • ST0683AU - Chris O'Brien Lifehouse
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
• Korea, Republic of
  • Seongnam, Korea, Republic of, 46370
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• New Zealand
  • Auckland, New Zealand, 1142
    • Starship Blood and Cancer Centre
• Portugal
  • Lisboa, Portugal
    • Instituto Português de Oncologia de Lisboa
• Sweden
  • Gothenburg, Sweden, 41650
    • Queen Silvia Children's Hospital
  • Linkoping, Sweden, 58185
    • HRH Crown Princess Victoria's Children and Youth Hospital
  • Stockholm, Sweden, S-171 77
    • Karolinska Institutet
  • Umea, Sweden, 901 85
    • Norrland University Hospital
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania School of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Up to 50 pediatric patients with ALK-aberrant neuroblastoma being treated with lorlatinib as part of expanded access program will be included.

Description

Inclusion Criteria:

• Patient receives lorlatinib through Pfizer's expanded access program for treatment of ALK+ neuroblastoma.
• HCP documentation of at least one tumor assessment of response after patient has had at least one dose of lorlatinib
• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Any patient who does not meet any of the inclusion criteria defined in the previous section.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric Neuroblastoma Patients Treated with Lorlatinib	Drug: lorlatinib; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue)	Tumor response was collected by the data collection tool (DCT) and responses included complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). As per International Neuroblastoma Response Criteria (INRC): CR=<10 millimeter (mm) residual soft tissue at primary site and complete resolution of metaiodobenzylguanidine (MIBG) or [18F] fluorodeoxyglucose (FDG)/positron emission tomography (PET) uptake (for MIBG-nonavid tumors) at primary site; PR: >=30% decrease in longest diameter (LD) of primary site & MIBG or FDG-PET uptake at primary site stable, improved, or resolved; SD: neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. PD greater than 20% increase in longest diameter taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study) and minimum absolute increase of 5 mm in longest dimension. One participant may have more than one tumor response.	From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis	Tumor response collected by DCT.Response included CR=resolution of all sites of disease; PR:>=30% decrease in sum of diameter of non-primary (NP) target lesion (TL) compared to baseline, non-target (NT) lesion may be stable/small in size, no new lesion,>=50% reduced MIBG absolute(abs) bone score (BS) (relative MIBG BS>=0.1 to <=0.5)/>=50% reduced number of FDG-PET avid bone lesion; PD:new soft tissue lesion (STL) detected by computed tomography (CT)/magnetic resonance imaging (MRI) that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied, confirmed as neuroblastoma(NB)/ganglioneuroblastoma(GNB),new bone site:MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor/confirmed histologically as NB/GNB; >20% increase in LD as reference smallest sum on study,minimum abs. increase of 5mm in sum of diameter of target STL; SD:No sufficient (suff) shrinkage for PR/suff increase for PD of NP lesion.One participant may have more than 1 tumor response	From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants According to Bone Marrow Response	Bone marrow response was collected by the DCT and responses included CR, PR, minimal disease (MD) and SD. As per INRC, CR= bone marrow with no tumor infiltration upon reassessment, independent of baseline tumor involvement; PD= bone marrow without tumor infiltration that became > 5% tumor infiltration upon reassessment; or bone marrow with tumor infiltration that increased by > 2 fold and had > 20% tumor infiltration upon reassessment; MD= Bone marrow with less than or equal to (<=) 5% tumor infiltration and remained > 0 to <= 5% tumor infiltration upon reassessment; or bone marrow with no tumor infiltration that became <= 5% tumor infiltration upon reassessment; or bone marrow with >20% tumor infiltration that had > 0 to <= 5% tumor infiltration upon reassessment and SD= bone marrow with tumor infiltration that remained positive with > 5% tumor infiltration upon reassessment but did not meet CR, MD or PD criteria.	From start of lorlatinib treatment until CR, PR, MD or SD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants According to Health Care Professional (HCP) Reported Objective Response	Objective response was collected by the DCT and comprised of responses in 3 components based on INRC: primary tumor, soft tissue and bone metastases and bone marrow, CR=All components met criteria for CR; PR=PR in at least one component and all other components are either CR, MD (bone marrow), PR (soft tissue or bone), or not involved (NI); no component with PD; Minor response (MR) = PR or CR in at least one component but at least one other component; no component with PD; SD= SD in one component with no better than SD or NI in any other component; PD=Any component with PD. One participant may have more than one tumor response.	From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants According to Derived Objective Response	Derived objective response was derived using rules based on responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD = Any component with PD.	From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants With Best Overall Response Based on HCP Reported Objective Response	Best overall response based on HCP reported objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=At least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = It is in one component with no better than SD or NI in any other component PD = Any component with PD. Best overall response taking the HCP reported response observed up to the data cut-off date for a specific milestone.	From start of lorlatinib treatment until CR, PR, MR, SD or PD, Up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Number of Participants With Best Overall Response Based on Derived Objective Response	Best overall response based on derived objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR= PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD= Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD= Any component with PD.	From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Overall Response Rate Based on HCP Reported Response	Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). Two sided 95% confidence interval was based on Clopper Pearson method.	From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Overall Response Rate Based on Derived Response	Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD).	From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Duration of HCP Reported Overall Responses	Duration of HCP reported overall response was derived as (earliest date of disease progression or death minus earliest date of complete or partial response + 1)/30.4. Participants who had not progressed or died were censored at their last assessment date prior to the data cut-off date. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved. PD=Any component with PD.	From date of CR or PR until earliest date of PD or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Progression Free Survival (PFS)	PFS was derived as (date of PD or death [by any cause in the absence of PD] minus date of first dose of lorlatinib plus 1) divided by 30.4. Participants who had not progressed or died were censored at the date of last contact prior to the data cut-off date. PD: new soft tissue lesion (STL) detected by CT/MRI that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied and confirmed as neuroblastoma (NB)/ganglioneuroblastoma (GNB), new bone site: MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor or confirmed histologically as NB/GNB; >20% increase in LD as reference smallest sum on study (included baseline sum if that was the smallest on study), minimum abs increase of 5mm in sum of diameter of target STL.	From start of lorlatinib treatment until disease progression or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Duration of Treatment	Duration of treatment was derived as treatment stop date minus treatment start date plus 1. Participants continuing treatment at the data cut-off date were censored based on the last recorded date when the participant was known to be continuing treatment prior to the data cut-off date.	From start of lorlatinib treatment until treatment stop date or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Overall Survival	Overall survival was derived as date of death minus treatment start date plus 1. Participants who had not died were censored at the date of last contact prior to the data cut-off date.	From date of first dose of lorlatinib until date of death or censoring date, up to maximum (max) of 36.2 months (M) of treatment (data was retrieved and evaluated retrospectively during approximately (approx.) 18 months of this study)
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events	An AE is any untoward medical occurrence in participants administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. A SAE is any untoward medical occurrence in a participant administered a medicinal or nutritional product at any dose that: resulted in death, was life-threatening, required participant hospitalization or prolongation of hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) and resulted in congenital anomaly/birth defect. Relatedness to treatment was determined by investigator.	From start of first dose of lorlatinib/date of informed consent(participant treated with lorlatinib) to atleast 28 day after last dose of lorlatinib to max 36.2M of treatment(data was retrieved, evaluated for approx. 18 month)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma
• Other Study ID Numbers: B7461036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.