Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

mpMRI, and if suspect MR-targeted prostate biopsy, in men with increased PC risk as judged from the STHLM3 test and/or an elevated prostate specific antigen test.

Men who request a prostate specific antigen test from their general practitioner will be offered study participation.

Men with increased PC risk as judged from the STHLM3 test and/or an elevated PSA test will be offered an mpMRI examination.

PSA, STHLM3 and mpMRI for PC detection

Bodil G. Pedersen, MD, PhD

Karina D. Sørensen, Professor

Prostate cancer (PC) is the most common malignancy (4500 new cases/year) and the second leading cause of cancer-associated mortality (1200 deaths/year) among men in Denmark. PC is generally diagnosed on the basis of an elevated prostate specific antigen blood test followed by transrectal ultrasound (TRUS)-guided prostate biopsy.

This study aims to test early detection of PC in general practice, using the STHLM3 model with superior specificity and sensitivity for clinically significant PC, combined with multiparametric magnetic resonance imaging (mpMRI) of the prostate and MR guided biopsy.

While early stage PC can be cured by surgery or radiation therapy, advanced PC is incurable and associated with high morbidity and mortality. Early detection is critical to save lives, but many newly diagnosed PCs are in reality non-aggressive and will not affect the patient's life or health, even if left untreated. There is an urgent need to replace current clinical practice with a more accurate diagnostic approach that can ensure early detection of aggressive PC while curable, reduce unnecessary prostate biopsies incl. risk of sepsis and reduce overdiagnosis/-treatment of indolent PC.

New molecular biomarkers applied in general practice, serving as a pre-selection test for follow-up, and accurate and patient-friendly MR-imaging and MR-targeted biopsy at the hospital may help to solve these problems.

In this study the investigators will assess the clinical utility of combining genetic risk testing and plasma protein markers (STHLM3 test) in general practice with mpMRI and MR-guided in bore biopsy (MRGB) for early PC detection in a biopsy naïve population.

Early and Accurate Detection of Prostate Cancer in General Practice

Early and Accurate Detection of Prostate Cancer in General Practice Using Novel Molecular Biomarkers and Multiparametric MR Imaging.

Evaluation of the proportion of patients identified with PC suspicious lesions at mpMRI based on the STHLM3 vs. the prostate specific antigen test.

Evaluation of the proportion of total PCs and clinically significant PCs diagnosed with MR guided biopsy as a function of the primary tests.

Comparison of the results from the clinical study with the number of prostate specific antigen tests, TRUS-biopsies, indolent and significant PCs detected by current clinical practice, using health register data from general practices not taking part in the trial.

Regional Hospital Holstebro

University of Aarhus

Central Denmark Region

Karolinska Institutet

Karolinska University Hospital

Aarhus University Hospital

Symptoms and General Pathology

Rare Diseases

Recurrence

Medulloblastoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Medulloblastoma, Childhood

Neuroepithelioma

Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board

Specialized Tumor Board Treatment Plan

Aubrie Drechsler

Ashley Margol, MD

Tom Davidson, MD

John Crawford, MD, MS

Jennifer Elster, MD

Krystal Pryor

Sabine Mueller, MD, PhD

Alyssa Reddy, MD

Lindsay Kilburn, MD

Roger Packer, MD

Mohamed AbdelBaki, MD

Margaret Shatara, MD

Cassie Kline, MD, MAS

Jane Minturn, MD, PhD

Sabine Mueller, MD, PhD, MAS

Joshua Rubin, MD, PhD

Robert Wechsler-Reya, PhD

Megan Paul, MD

The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility of performing real-time drug screening on tissue taken during surgery, and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with medulloblastoma to receive the most effective and least toxic therapies currently available, and will pave the way for improved understanding and treatment of these tumors in the future.

This is a single arm multi-center pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). Relapsed participants will receive an individualized treatment recommendation including up to four FDA-approved drugs based on the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

PRIMARY OBJECTIVE:

I. To determine the feasibility of using the results of real-time in vitro drug screening, whole exome sequencing, and RNA sequencing of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma.

SECONDARY OBJECTIVE:

I. To determine the safety and describe the toxicity of treating children and young adults with relapsed medulloblastoma according to a specialized tumor board that makes treatment recommendations based on real-time drug screening and genomic sequencing.

EXPLORATORY OBJECTIVES:

I. To estimate the objective response rate, progression free survival at 6 months (PFS-6) and overall survival (OS) of relapsed medulloblastoma in children and young adults treated with an individualized treatment regimen.

II. To assess Quality of Life (QOL) measures in participants with relapsed medulloblastoma treated with an individualized regimen.

III. To archive tumor and normal DNA from each participant along with serial blood draw following therapies as biospecimens for later studies to determine whether circulating tumor DNA (ctDNA) sequences in the participant's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance.

Participants may continue treatment as tolerated for up to two years or until disease progression. Participants will be followed until progression, death, or up to 5 years from start of therapy.

Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma

A Pilot Trial of Real Time Drug Screening and Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma

Individual participant data after de-identification.

Time to tissue collection will be used to determine the feasibility of using the results of real-time in vitro drug screening, WES and RNAseq of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma. Participants are expected to receive treatment plan within 21 business days

Proportion of participants with grade 3 or higher toxicities classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3 or higher criteria will be summarized by maximum grade and relationship to study drug(s).

Washington University School of Medicine

St. Baldrick's Foundation

Ashion Analytics

University of Washington

Pacific Pediatric Neuro-Oncology Consortium

University of California, San Francisco

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Syndrome

Colonic Neoplasms

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Central Nervous System Stimulants

All Drugs and Chemicals

Other Dietary Supplements

Herbal and Botanical

Caffeine

Cola

All individuals in the intervention arm who consent to participate in the HNPCC screening will have their tumors evaluated for MSI following surgery. Those with MSI-H results will receive a genetic counseling informational call.

These patients will be treated as usual by their oncologist and medical team. These patients receive a follow up letter a year after randomization, alerting them to the availability of clinical Lynch Syndrome screening.

All individuals in the intervention arm who consent to participate in the HNPCC screening will have their tumors evaluated for MSI.

MSI screening test

Katrina AB Goddard, PhD

The investigators research mobilizes the resources of an integrated health-delivery system with extensive electronic clinical data to implement and evaluate a new strategy to maximize screening of Colorectal Cancer (CRC) patients for Lynch Syndrome.

Screening tests for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) \[also called Lynch Syndrome\], are among the few available validated genetic tests that have been recommended as an evidence-based practice that can save lives. However, more than half of patients who meet well-established and accepted screening criteria do not receive screening. This is a critical failure for patients and for the health-care delivery system because HNPCC mutation carriers are at exceptionally high risk for colorectal and other HNPCC-related cancers, and because clinical strategies can prevent future cancers, or provide early detection, for individuals affected with HNPCC and their relatives. HNPCC testing is also cost-effective compared to treating individuals with a diagnosis of colorectal cancer (CRC).

To address this shortfall in practice, our proposed research mobilizes the resources of an integrated health-delivery system with extensive electronic clinical data to implement and evaluate a new strategy to maximize screening of CRC patients for HPNCC. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group recommended that all newly diagnosed CRC patients be screened for HPNCC, but was not able to recommend a best-strategy to accomplish this aim. Therefore, using the Practical Robust Implementation and Sustainability Model (PRISM), developed by one of our co-investigators, to guide the analyses, the investigators will:

Aim #1: Conduct a randomized controlled trial to determine the effectiveness of a universal laboratory test-based HNPCC screening program compared to the current practice of physician referral and self-referral.

Aim #2: Elucidate patient, provider, and system factors important to success of implementation.

Aim #3: (revised and approved during year 1): To create, refine, and disseminate an implementation guide for HNPCC screening by combining the results from Aims 1-2 and the perspectives from informant interviews of key staff at future diverse dissemination-implementation sites: Case Western Reserve University, Oregon Health \& Sciences University, MD Anderson Cancer Center, Dana-Farber Cancer Institute, Kaiser Permanente Georgia, Kaiser Permanente Hawaii, and Safety Net West Clinics. Addition to Aim 3: We will contribute materials to the LSSN website for dissemination of implementation materials.

This study aims to evaluate implementation of a novel HNPCC screening program and assess, for all stakeholders, facilitators and barriers to program implementation and success. Results from this study will help achieve the Healthy People 2020 objective of reducing CRC mortality. It will add to the growing literature in the increasingly important area of translating research findings into real-world practice, a subject of the NIH Roadmap. Many of the findings will be useful in other clinical areas and will be broadly applicable to other health care organizations aiming to improve access to genetic tests for cancers.

Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting

The primary outcomes to assess implementation effectiveness are: number of patients who receive HNPCC screening test results; number of physicians who receive their patients HPNCC screening test results; completion of the educational session at three months of follow-up; and number of patients with MSI-H (microsatellite instability-high) test results who are contacted by medical genetics.

Case Western Reserve University

M.D. Anderson Cancer Center

Dana-Farber Cancer Institute

Vanderbilt University

Kaiser Permanente

At least 40 SNP (single nucleotide polymorphisms)increase the risk of PCa. The individual risk of PCa accumulates with the increasing number of these genetic variants. The risk is doubled if patient has familial disposition as well. In retrospective studies, non-genetic risk-prediction models were compared to risk-prediction models containing both non-genetic factors and SNPs analyses. The genetic models had a significantly higher specificity than the non-genetic models. It has been argued that genetic PCa risk assessment could reduce the inexpedient use of PSA tests, saving it for patients at high risk of PCa.

Genetic risk assessment

Karina D Sørensen, PhD

Flemming Bro, Professor

Peter Vedsted, Professor

The preferred method for early detection of prostate cancer (PCa) in older men with family history is the Prostate Specific Antigen test (PSA test), although the method is imprecise. It produces a high number of false-positive results and increases the risk of over-diagnosis and over-treatment. Yet, an increasing number of men get the PSA test as part of unsystematic screening. Genetic risk assessment may be a better way to identify men with low risk of PCa. The main study hypothesis is that genetic information about low risk of PCa can reduce the number of patients who get a PSA test as part of unsystematic screening.

The ProCaRis Study: Prostate Cancer Risk Assessment in General Practice

Prostate Cancer Risk Assessment Using Genetic Markers in General Practice

The primary objective of this study is to evaluate the impact on use of PSA tests of introducing genetic PCa risk assessment in general practice.

Velux Fonden

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Thyroid Neoplasms

Thyroid Diseases

Pheochromocytoma

Paraganglioma

Osteosarcoma

Bone Neoplasms

Kidney Neoplasms

Disease Susceptibility

Neuroendocrine Tumors

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Bone Diseases

Paragangliomas 1

Neuroendocrine Tumor

Germline and/or tumor samples will be screened for mutations

Genetic screening

Patricia L Dahia, MD,PhD

Patricia L Dahia

Patricia L Dahia, MD, PhD

Pheochromocytomas and paragangliomas are neural crest-derived tumors of the nervous system that are often inherited and genetically heterogeneous. Genetic screening is recommended for patients and their relatives, and can guide clinical decisions. However, a mutation is not found in all cases. The aims of this proposal are to: 1) to map gene(s) involved in pheochromocytoma, and 2) identify genotype-phenotype correlations in patients with pheochromocytoma/paraganglioma of various genetic origins.

Pheochromocytoma and paragangliomas are tumors originated from neuroectoderm cells located in the adrenal or extra-adrenal paraganglia, often leading to increased secretion of hormones known as catecholamines. These tumors represent a potentially curable cause of hypertension and are malignant in about 10-15% of the cases. Approximately 40% of patients with pheochromocytomas and/or paraganglioma have an inherited mutation. In addition, some patients and/or their relatives that are mutation carriers can develop other tumors as part of inherited cancer susceptibility syndromes. Therefore, detection of the susceptibility mutation is important for diagnosis and follow up. However, the susceptibility gene mutation cannot be identified in all cases. Studies that aim to identify novel susceptibility genes for pheochromocytoma are required.

The fist aim of this study is to identify novel pheochromocytoma susceptibility genes. Characterization of such gene(s) can improve our understanding of the pathogenesis pheochromocytoma and paraganglioma and have an impact in diagnosis, therapeutic planning and genetic screening of relatives.

The second aim of this project is to characterize relationships between mutations and clinical features that can provide insights into clinical surveillance and screening of at-risk individuals.

Samples from affected individuals will be obtained as:

* DNA from peripheral blood lymphocytes,
* DNA from tumor tissue, or
* Frozen peripheral blood lymphocytes for nucleic acid purification
* Frozen tumor tissue for nucleic acid purification
* Lymphoblastoid cell lines, if available
* Buccal cells obtained by cheek swab or saliva

Samples from unaffected relatives will be obtained as:

* DNA from peripheral blood lymphocytes, or
* Frozen peripheral blood lymphocytes for nucleic acid purification

Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

Aggregate data will be available in the form of publications and pertinent data will be deposited in public depositories

Genetic screen detects a mutation that is likely responsible for tumor development

Genetic screen detects other mutations with potential pathogenic effects

Clinical data reveals other features that might associate with the main disease phenotype

National Institute of General Medical Sciences (NIGMS)

The University of Texas Health Science Center at San Antonio

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early and Accurate Detection of Prostate Cancer in General Practice	NCT03431753	Prostate Cancer Prostate Neopla... Prostate Adenoc...	PSA, STHLM3 and...	50 Years - 69 Years	University of Aarhus
Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma	NCT05057702	Medulloblastoma Medulloblastoma... Medulloblastoma...	Specialized Tum...	12 Months - 39 Years	University of California, San Francisco
Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting	NCT01582841	Colon Cancer Lynch Syndrome	MSI screening t...	18 Years -	Kaiser Permanente
The ProCaRis Study: Prostate Cancer Risk Assessment in General Practice	NCT01739062	Prostate Cancer	Genetic risk as...	18 Years - 80 Years	University of Aarhus
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions	NCT03160274	Pheochromocytom... Paraganglioma Inherited Cance... Associated Cond... Kidney Neoplasm... Bone Cancer Thyroid Neoplas... Other Cancer	Genetic screeni...	-	The University of Texas Health Science Center at San Antonio

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