Ignite Creation Date:
2024-05-05 @ 4:54 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00340522
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2006-06-19
Brief Title:
Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development
Status:
COMPLETED
Status Verified Date:
2014-08-11
Last Known Status:
None
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:
This study will construct tissue microarrays TMAs pertaining to childhood cancer TMA technology is a recently developed one that allows for evaluating hundreds of tissue samples simultaneously on the DNA RNA and protein levels The goal is to identify a potential molecular signature Cancer drug discovery is currently focused on identifying drugs targeted at the molecular level Such drugs would be more selective and specific for proteins and signaling pathways that are directly involved in the origin of tumors However the origin of cancer among adults differs from that of cancer diagnosed in children The overall approach by the pharmaceutical industry in developing drugs is not likely to be aimed at low-incidence cancers such as childhood cancers Thus the researchers in this study propose to create a childhood cancer TMA that include specimens from a wide range of solid tumors that present a poor prognosis for patients This TMA would in turn be used to identify antibodies and lead to developing molecularly targeted drugs that would reach clinical trials in adults
TMAs are created robotically Small tissue cores are taken from paraffin-embedded tissue blocks and are implanted into new paraffin blocks The recipient blocks are then processed to produce several hundred specimens that can be evaluated on a single glass slide Specimens representing 17 distinct kinds of pediatric solid tumors will be used in this study Also included will be samples of plexiform neurofibroma-that is benign growths of nervous and connective tissues
Tissue specimens will come from patients who were age 25 or younger at the time of diagnosis of their cancer or plexiform neurofibroma No procedures will be performed for the sole purpose of obtaining tissue for this study
The TMA developed in this study will not be commercialized The results for individuals whose tumor specimens are used in the array will not be sent to patients or their treating physicians
TMAs are created robotically Small tissue cores are taken from paraffin-embedded tissue blocks and are implanted into new paraffin blocks The recipient blocks are then processed to produce several hundred specimens that can be evaluated on a single glass slide Specimens representing 17 distinct kinds of pediatric solid tumors will be used in this study Also included will be samples of plexiform neurofibroma-that is benign growths of nervous and connective tissues
Tissue specimens will come from patients who were age 25 or younger at the time of diagnosis of their cancer or plexiform neurofibroma No procedures will be performed for the sole purpose of obtaining tissue for this study
The TMA developed in this study will not be commercialized The results for individuals whose tumor specimens are used in the array will not be sent to patients or their treating physicians
Detailed Description:
Background Cancer drug discovery is now focused on identifying molecularly targeted drugs that are more selective and specific for proteins and signaling pathways that are directly involved in tumorigenesis This new paradigm alters the approach to clinical drug development for childhood cancers because the emphasis is on therapeutic targets present in common epithelially-derived adult cancers which have a different pathogenesis The pharmaceutical industry is unlikely to undertake target discovery programs for low incidence cancers such as childhood cancers Therefore a more pragmatic approach to the development of molecularly targeted drugs in children is required
Objective Construct a childhood cancer tissue microarrays TMA for screening and selecting the most appropriate molecularly targeted agents for clinical development in childhood cancers
Eligibility Ten to twenty representative specimens paraffin blocks for each of 25 histologically distinct pediatric solid tumors or plexiform neurofibromas will be collected
Design Using a robotic arrayer three 06 mm cores from each tissue block will be donated into one of 3 recipient paraffin TMA blocks CNS tumors sarcomas embryonal tumors Standard immunohistochemical techniques will be applied to 5 micro m sections from the TMA block using validated antibodies directed against specific protein targets of interest If greater than 8 to 20 tumors from each specific histological type of cancer are positive there is a 95 probability that the true proportion of positive specimens exceeds 20 The results of the TMA target assessment will guide in the selection of molecularly targeted drugs for pediatric phase I clinical trials in the POB and Pediatric Phase IPilot Consortium and the selection of candidate tumors for activity testing in phase II clinical trials If clinical responses are observed in phase I or II trials in tumor types that express the target on the TMA we will return to the original paraffin blocks and perform Laser Capture Microdissection and produce reverse-phase lysate protein microarrays to assess the activation state of targeted signaling pathways and investigate the role of the target protein in tumorigenesis of the responsive childhood cancers
Objective Construct a childhood cancer tissue microarrays TMA for screening and selecting the most appropriate molecularly targeted agents for clinical development in childhood cancers
Eligibility Ten to twenty representative specimens paraffin blocks for each of 25 histologically distinct pediatric solid tumors or plexiform neurofibromas will be collected
Design Using a robotic arrayer three 06 mm cores from each tissue block will be donated into one of 3 recipient paraffin TMA blocks CNS tumors sarcomas embryonal tumors Standard immunohistochemical techniques will be applied to 5 micro m sections from the TMA block using validated antibodies directed against specific protein targets of interest If greater than 8 to 20 tumors from each specific histological type of cancer are positive there is a 95 probability that the true proportion of positive specimens exceeds 20 The results of the TMA target assessment will guide in the selection of molecularly targeted drugs for pediatric phase I clinical trials in the POB and Pediatric Phase IPilot Consortium and the selection of candidate tumors for activity testing in phase II clinical trials If clinical responses are observed in phase I or II trials in tumor types that express the target on the TMA we will return to the original paraffin blocks and perform Laser Capture Microdissection and produce reverse-phase lysate protein microarrays to assess the activation state of targeted signaling pathways and investigate the role of the target protein in tumorigenesis of the responsive childhood cancers
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-N282 | None | None | None |