Ignite Creation Date:
2024-05-06 @ 2:11 AM
Last Modification Date:
2024-10-26 @ 11:15 AM
Study NCT ID:
NCT01986595
Status:
UNKNOWN
Last Update Posted:
2013-11-18
First Post:
2013-11-04
Brief Title:
A Pilot Study on ALK Gene Mutations in Neuroblastoma
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
A Pilot Study on ALK Gene Mutations in Neuroblastoma
Status:
UNKNOWN
Status Verified Date:
2013-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Neuroblastoma NB originates from the sympathetic nervous system and is one of the most common cancers in infants and children In our hospital nearly 70 of patients are diagnosed with stage 4 metastatic disease with a poor prognosis despite the use of multimodal therapy including chemotherapy surgery autologous stem cell transplantation radiation therapy and differentiation therapy To improve the survival rate and patient care our NB Study Group has devoted to the research on NB-specific molecular imaging biomarkers and target therapy We have confirmed studies in cancer genetics by showing that N-myc gene MYCN amplification and segmental abnormalities on overall genomic profiling both have an adverse effect on treatment outcome Therefore there is an unmet need for the development of novel molecular target therapy in NB Recently the anaplastic lymphoma kinase ALK oncogene has been found to play an important role in the pathogenesis of NB as well as serving as the driver mutations in approximately 10 of high-risk NB The availability of ALK inhibitors also enables ALK as a treatment target in NB In this proposal we plan to utilize gene sequencing array-comparative hybridization and multiplex ligation-dependent probe amplification methods to evaluate the frequencies and characteristics of ALK mutations and amplifications in patients with NB The gene and protein expression of ALK will also be evaluated by quantitative polymerase chain reactionPCR and immunohistochemistry respectively and compared with ALK genotype The overall genomic pattern clinical characteristics histopathology and treatment outcome of ALK-mutated NB patients will be analyzed The results from this study may serve as the first report on ALK mutations of NB in Taiwan and will be used for the development of standardized genetic diagnosis protocols as well as the design of future clinical trials targeting ALK
Detailed Description:
purpose Despite the advance of modern multimodal therapy including surgery chemotherapy autologous stem cell transplantation radiation therapy and differentiation therapy most children with NB are diagnosed with metastatic diseases and suffer from a dismal outcome There is an unmet need for the development of novel target therapy in NB Among all recently identified targets ALK gene mutations have been found in approximately 10 of high-risk NB patients and are the treatment target of several promising agents that have already been tested in clinical trials including crizotinib which is to be available in Taiwan soon This study aims to evaluate the prevalence of mutations and copy number aberrations of the ALK oncogene in prospective and previously treated NB patients tumor sample from surgical specimens and germ-line peripheral blood lymphocytes The messenger ribonucleic acidmRNA and protein expression levels of ALK will also be analyzed The results will be correlated with the clinical characteristics and pathological findings of this NB cohort
technique Prospective cases Cryopreservation of tumor samples Retrospective cases Archived tumor Sequencing point mutation array-based comparative genomic hybridizationaCGH MLPAmultiplex ligation-dependent probe amplificationanalyze copy number alterations CNAs compare to clinical data
expected results The results from this study may serve as the first report on ALK gene mutations of NB in Taiwan We anticipate that 5-15 of NB tumors carry with common ALK mutations Genome-wide CNAs profiling by aCGH can help us to categorize the genomic types of NB patients based on published guidelines while the presence of ALK mutation or amplification may or may not be associated with subtypes with worse outcome Some patients may have high ALK expression level without bearing common mutations on ALK gene locus and we may identify novel mutation points in this patient cohort Finally we will probably find significant prognostic value of ALK gene mutation which may be independent from other known risk factors such as age stage MYCN amplification and genomic pattern
Based on these results we are able to develop standardized protocol for diagnosing ALK mutations for Taiwanese NB patients With the development of ALK genetic testing a phase II clinical trial of an ALK inhibitor in high-risk NB patients with relapsed or refractory disease may subsequently be conducted and may improve the treatment outcome of the patients
technique Prospective cases Cryopreservation of tumor samples Retrospective cases Archived tumor Sequencing point mutation array-based comparative genomic hybridizationaCGH MLPAmultiplex ligation-dependent probe amplificationanalyze copy number alterations CNAs compare to clinical data
expected results The results from this study may serve as the first report on ALK gene mutations of NB in Taiwan We anticipate that 5-15 of NB tumors carry with common ALK mutations Genome-wide CNAs profiling by aCGH can help us to categorize the genomic types of NB patients based on published guidelines while the presence of ALK mutation or amplification may or may not be associated with subtypes with worse outcome Some patients may have high ALK expression level without bearing common mutations on ALK gene locus and we may identify novel mutation points in this patient cohort Finally we will probably find significant prognostic value of ALK gene mutation which may be independent from other known risk factors such as age stage MYCN amplification and genomic pattern
Based on these results we are able to develop standardized protocol for diagnosing ALK mutations for Taiwanese NB patients With the development of ALK genetic testing a phase II clinical trial of an ALK inhibitor in high-risk NB patients with relapsed or refractory disease may subsequently be conducted and may improve the treatment outcome of the patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None