Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00340522
First received: June 19, 2006
Last updated: September 10, 2014
Last verified: August 2014
  Purpose

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.


Condition
Cancer

Study Type: Observational
Official Title: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 20
Study Start Date: September 2004
Estimated Study Completion Date: August 2014
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 0.6 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 I/Pilot 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.

  Eligibility

Ages Eligible for Study:   up to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Twenty representative formalin-fixed, paraffin-embedded specimens for each of 17 histologically distinct pediatric solid tumors will be collected from the pathology departments of selected Pediatric Phase I Consortium collaborators.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00340522

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Brigitte C Widemann, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00340522     History of Changes
Other Study ID Numbers: 999904282, 04-C-N282
Study First Received: June 19, 2006
Last Updated: September 10, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Sarcoma
Brain Tumor
Embryonal Tumor
Tumor Array
Childhood Cancer
Plexiform Neurofibromas
Drug Screening
Immunohistochemistry

Additional relevant MeSH terms:
Neurofibroma
Neurofibroma, Plexiform
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nerve Sheath Neoplasms
Nervous System Diseases
Nervous System Neoplasms
Neuromuscular Diseases
Peripheral Nervous System Diseases
Peripheral Nervous System Neoplasms

ClinicalTrials.gov processed this record on October 30, 2014