Real World Data Collection Pediatric Neuroblastoma Treated With Lorlatinib

NCT04753658 | Terminated Results

• 1 other identifier: B7461036
• Study Type: observational
• Target: 15
• Locations: 6 countries
• Sites: 11

Brief Summary

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.

Conditions

Neuroblastoma

Outcome Measures

Primary Outcomes (14)

• 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)

Study Arms (1)

Pediatric Neuroblastoma Patients Treated with Lorlatinib

Drug: lorlatinib

Interventions

lorlatinib DRUG

Oral

Pediatric Neuroblastoma Patients Treated with Lorlatinib

Eligibility Criteria

• Age: 0 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (11)

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

ST0683AU - Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050 Australia, Australia

Location

Starship Blood and Cancer Centre

Auckland, 1142, New Zealand

Location

Instituto Portugues de Oncologia de Lisboa

Lisbon, Portugal

Location

Seoul National University Bundang Hospital

Seongnam, 46370, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Queen Silvia Children's Hospital

Gothenburg, 41650, Sweden

Location

HRH Crown Princess Victoria's Children and Youth Hospital

Linköping, 58185, Sweden

Location

Karolinska Institutet

Stockholm, S-171 77, Sweden

Location

Norrland University Hospital

Umeå, 901 85, Sweden

Location

Related Links

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

MeSH Terms

Conditions

Neuroblastoma

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 15, 2021
• Study Start: March 19, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); PT (1); SE (4); KR (2); US (1); NZ (1)