Neoplasms

All Conditions

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Brain Neoplasms

Neurofibromatoses

Neurofibroma

Neurofibroma, Plexiform

Neurofibromatosis 1

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Soft Tissue Sarcoma

Neurofibromatosis

Neurofibromatosis Type 1

Brigitte C Widemann, M.D.

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.

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.

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

National Cancer Institute (NCI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Carcinoma

Prostatic Neoplasms

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Testicular Neoplasms

Kidney Neoplasms

Penile Neoplasms

Urologic Neoplasms

Neoplasms, Glandular and Epithelial

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Endocrine Gland Neoplasms

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Penile Diseases

Renal Cell Carcinoma

Transitional Cell Carcinoma

Penile Cancer

This is a prospective "n-of-1" type of trial where every patient is his/her own control. This is a study further developing the translational use of an existing framework and infrastructure for systematic sample collection an analytics previously established in the HUB project incorporating NGS and DSRT into clinical care.

Personalised treatment

Antti S Rannikko, MD, PhD

Antti s Rannikko, MD, PhD

Östling Päivi, PhD

Tuomas Mirtti, PhD

Petri Bono, PhD

Harry Nisen, PhD

Katriina Peltola, PhD

Olli Kallioniemi, PhD

Jukka Sairanen, PhD

Petrus Järvinen, PhD

Henrikki Santti, PhD

Anssi Petas, PhD

Mika Matikainen, PhD

Riikka Järvinen, PhD

Hanna Vasarainen, PhD

Tuomas Kilpeläinen, PhD

Mauri Kouri, PhD

Tapio Utriainen, PhD

Kimmo Taari, PhD

Vesa Rahkama, MSc

Andrew Erickson, MSc

Saeed Khalid, MSc

Maija Puhka, PhD

Vilja Pietiäinen, PhD

Lassi Paavolainen, MSc

Dmitry Bykhov, MSc

Teijo Pellinen, PhD

Sami Blom, MSc

Taija af Hällström, PhD

Kevin Sandeman, MD

Anu Kenttämies, PhD

Outi Oksanen, MD

Jarkko Pajarinen, PhD

Jari Siironen, PhD

The purpose of the study is to evaluate whether state-of-the-art technologies such and next generation sequencing and drug sensitivity and resistance testing of patient derived tumour tissue can facilitate research translation and improve outcome of urologic cancers.

Access to high-quality clinical patient material (e.g. tissue of primary tumor and metastasis, plasma and urine) linked to comprehensive registry and clinical data and molecular characterization of the patient material using state-of-the-art technologies (e.g. NGS, transcriptomics, imaging, DSRT) will facilitate a more rapid translation of basic research innovations into clinical care (diagnostics, imaging, therapeutics) and result in improved outcome of patients suffering from urologic cancers ("personalized medicine").

The principal aim of the project is to establish a framework and infrastructure for the systematic collection and interpretation of biological patient samples. Similarly, the investigators aim to establish the format how the related clinical and research data can be made readily accessible for both clinicians and researchers without compromising patient privacy. The key objectives of the project are to facilitate research translation and to improve outcome of urologic cancers.

Development of Diagnostics and Treatment of Urological Cancers

The magnitude of successful clinical translation is measured by the number of times project-derived personalized medicine has impacted patients care by application of novel and existing biomarkers and therapies (e.g. sequencing, DSRT) by 2020

Successful pre-clinical translation, the magnitude of which is measured by the number of times project-derived potential druggable targets or able to re-purpose treatment options were identified within the project by 2020.

Translation of preclinical data into clinically useful data. The success of which is measured by the number of times preclinical data (e.g. sequencing, DSRT) was transformed into clinically useful form within 4 weeks from the time the initial sampling of the specimen was done.

Representativeness is based on the genetics of the cell model and the parental tumor

Karolinska Institutet

Helsinki University Central Hospital

Senior consultant, urology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development	NCT00340522	Cancer		- 25 Years	National Institutes of Health Clinical Center (CC)
Development of Diagnostics and Treatment of Urological Cancers	NCT02994758	Prostate Carcin... Kidney Cancer Urothelial Carc... Testicular Canc... Penile Cancer	Personalised tr...	18 Years -	Helsinki University Central Hospital
Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development	NCT00340522	Cancer		- 25 Years	National Institutes of Health Clinical Center (CC)
Development of Diagnostics and Treatment of Urological Cancers	NCT02994758	Prostate Carcin... Kidney Cancer Urothelial Carc... Testicular Canc... Penile Cancer	Personalised tr...	18 Years -	Helsinki University Central Hospital

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