NCT04753658

Real World Data Collection Pediatric Neuroblastoma Treated With Lorlatinib

Terminated Results posted Last updated 23 September 2024

What this trial tests

trial testing lorlatinib in Neuroblastoma in 15 participants. Terminated before completion.

Timeline

19 March 2021

Primary endpoint
30 September 2022

30 September 2022

Quick facts

Lead sponsor	Pfizer
Status	Terminated
Study type	OBSERVATIONAL
Enrollment	15
Start date	19 March 2021
Primary completion	30 September 2022
Estimated completion	30 September 2022
Sites	11 locations across New Zealand, Sweden, South Korea, Australia, Portugal, United States

Drugs / interventions tested

• lorlatinib (lorlatinib) — full drug profile →

Conditions studied

• Neuroblastoma — all drugs for Neuroblastoma →

Sponsor

Pfizer — full company profile →

Who can join

0 and older, any sex, with Neuroblastoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) Primary · 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)

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, impro

CR

Group	Value	95% CI
Lorlatinib	3

PR

Group	Value	95% CI
Lorlatinib	3

SD

Group	Value	95% CI
Lorlatinib	5

PD

Group	Value	95% CI
Lorlatinib	2

Missing

Group	Value	95% CI
Lorlatinib	7

Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis Primary · 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)

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)/ganglio

CR

Group	Value	95% CI
Lorlatinib	5

PR

Group	Value	95% CI
Lorlatinib	5

SD

Group	Value	95% CI
Lorlatinib	5

PD

Group	Value	95% CI
Lorlatinib	7

Missing

Group	Value	95% CI
Lorlatinib	2

Number of Participants According to Bone Marrow Response Primary · 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)

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

CR

Group	Value	95% CI
Lorlatinib	2

PR

Group	Value	95% CI
Lorlatinib	0

MD

Group	Value	95% CI
Lorlatinib	1

SD

Group	Value	95% CI
Lorlatinib	0

Missing

Group	Value	95% CI
Lorlatinib	12

Number of Participants According to Health Care Professional (HCP) Reported Objective Response Primary · 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)

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

CR

Group	Value	95% CI
Lorlatinib	5

PR

Group	Value	95% CI
Lorlatinib	7

MR

Group	Value	95% CI
Lorlatinib	1

SD

Group	Value	95% CI
Lorlatinib	5

PD

Group	Value	95% CI
Lorlatinib	9

Number of Participants According to Derived Objective Response Primary · 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)

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

CR

Group	Value	95% CI
Lorlatinib	2

PR

Group	Value	95% CI
Lorlatinib	0

MR

Group	Value	95% CI
Lorlatinib	0

PD

Group	Value	95% CI
Lorlatinib	8

Missing

Group	Value	95% CI
Lorlatinib	1

Not Evaluable

Group	Value	95% CI
Lorlatinib	4

Number of Participants With Best Overall Response Based on HCP Reported Objective Response Primary · 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)

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 componen

Group	Value	95% CI
Lorlatinib	5
Lorlatinib	3
Lorlatinib	1
Lorlatinib	3

Number of Participants With Best Overall Response Based on Derived Objective Response Primary · 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)

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 compo

Group	Value	95% CI
Lorlatinib	2
Lorlatinib	8
Lorlatinib	5

Overall Response Rate Based on HCP Reported Response Primary · 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 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.

Group	Value	95% CI
Lorlatinib	53.3	26.6 – 78.7

Overall Response Rate Based on Derived Response Primary · 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 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).

Group	Value	95% CI
Lorlatinib	13.3	1.7 – 40.5

Duration of HCP Reported Overall Responses Primary · 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)

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.

Group	Value	95% CI
Lorlatinib	21.7	2.0 – NA

Progression Free Survival (PFS) Primary · 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)

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% incr

Group	Value	95% CI
Lorlatinib	17.8	3.7 – NA

Duration of Treatment Primary · 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)

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.

Group	Value	95% CI
Lorlatinib	16.2	3.4 – 24.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lorlatinib

Serious: 6/15 (40%)

Deaths: 8/15

Serious adverse events (17 terms)

Reaction	System	Lorlatinib
Weight increased	Investigations	—
Hemiparesis	Nervous system disorders	—
Peripheral motor neuropathy	Nervous system disorders	—
Peripheral sensory neuropathy	Nervous system disorders	—
Spinal cord compression	Nervous system disorders	—
Pneumonia	Infections and infestations	—
Rhinovirus infection	Infections and infestations	—
Sepsis	Infections and infestations	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Hypothyroidism	Endocrine disorders	—
Primary hypogonadism	Endocrine disorders	—
Pyrexia	General disorders	—
Hyperlipidaemia	Metabolism and nutrition disorders	—
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Urinary retention	Renal and urinary disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (30 terms — click to expand)

Reaction	System	Lorlatinib
Blood cholesterol increased	Investigations	—
Weight increased	Investigations	—
Alanine aminotransferase increased	Investigations	—
Blood triglycerides increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—
Anaemia	Blood and lymphatic system disorders	—
Candida infection	Infections and infestations	—
Oedema peripheral	General disorders	—
Blood lactate dehydrogenase increased	Investigations	—
Gamma-glutamyltransferase increased	Investigations	—
Lymphocyte count decreased	Investigations	—
Platelet count decreased	Investigations	—
White blood cell count decreased	Investigations	—
Hypernatraemia	Metabolism and nutrition disorders	—
Hyperuricaemia	Metabolism and nutrition disorders	—
Cognitive disorder	Nervous system disorders	—
Fine motor delay	Nervous system disorders	—
Paraesthesia	Nervous system disorders	—
Peripheral sensory neuropathy	Nervous system disorders	—
Speech disorder developmental	Nervous system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Pyelonephritis	Infections and infestations	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	—
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	—
Ascites	Gastrointestinal disorders	—
Insomnia	Psychiatric disorders	—

Most-reported serious reactions: Weight increased, Hemiparesis, Peripheral motor neuropathy, Peripheral sensory neuropathy, Spinal cord compression, Pneumonia, Rhinovirus infection, Sepsis.

Data from ClinicalTrials.gov NCT04753658 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting Oncogenic Transcriptional Networks in Neuroblastoma: From N-Myc to Epigenetic Drugs.
   Ciaccio R, De Rosa P, Aloisi S, Viggiano M, et al · · 2021 · cited 16× · PMID 34884690 · DOI 10.3390/ijms222312883
2. Therapeutic Targeting of the Anaplastic Lymphoma Kinase (ALK) in Neuroblastoma-A Comprehensive Update.
   Brenner AK, Gunnes MW. · · 2021 · cited 16× · PMID 34575503 · DOI 10.3390/pharmaceutics13091427
3. Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.
   Musumeci F, Cianciusi A, D'Agostino I, Grossi G, et al · · 2021 · cited 9× · PMID 34885651 · DOI 10.3390/molecules26237069