A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer

A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer

Patrocinadores

Patrocinador principal: National Cancer Institute (NCI)

Fuente National Institutes of Health Clinical Center (CC)
Resumen breve

Background: - Prostate cancer is the most common cancer and the second leading cause of death in males in the United States with an estimated 191,930 new cases and 33,330 deaths in 2020. - There has been progress in identifying established risk factors for the development of prostate cancer, including genetic predisposition. The study of the molecular genetics of prostate cancer has identified pathogenic variants, such as BRCA1 and BRCA2 (associated with hereditary breast and ovarian cancer syndrome), HOXB13 (associated with hereditary prostate cancer), and DNA mismatch repair (MMR) gene variants (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome. - While our understanding of molecular genetics continues to grow, there remains a need to identify additional germline and somatic mutations and alterations that may increase an individual s risk to develop prostate cancer and potentially the aggressiveness of the disease. In studying the following alterations in prostate cancer, in both localized and advanced stages, potential expanded molecular findings may lead to actionable therapeutic targets and biomarker development. A better understanding of molecular genetics in a longitudinal study of subjects with prostate cancer may be helpful for the design of future treatment studies, and to develop a better understanding of the natural history of the disease Objectives: - To longitudinally evaluate subjects with prostate cancer with known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM to better understand the natural history of the disease. - To longitudinally evaluate subjects with tumor mutational burden-high (TMB-H) prostate cancer [greater than or equal to 10 mutations/megabase (mut/Mb)]. Eligibility: - Subjects with histologically confirmed prostate cancer - Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high or be deemed an exceptional responder. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified) - Age greater than or equal to 18 years old Design: - This will be a long-term multi-center study to comprehensively study participants with prostate cancer. - Participants will provide clinical information (including medical history, clinical tests, imaging studies and reports, surgical pathology reports, genetic test results). - Since long-term follow-up of individuals with prostate cancer is a major feature of the study, local sites intend to maintain active contact with study subjects for as long as possible. Participants will be followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies and duration of responses....

Descripción detallada

Background: - Prostate cancer is the most common cancer and the second leading cause of death in males in the United States with an estimated 191,930 new cases and 33,330 deaths in 2020. - There has been progress in identifying established risk factors for the development of prostate cancer, including genetic predisposition. The study of the molecular genetics of prostate cancer has identified pathogenic variants, such as BRCA1 and BRCA2 (associated with hereditary breast and ovarian cancer syndrome), HOXB13 (associated with hereditary prostate cancer), and DNA mismatch repair (MMR) gene variants (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome. - While our understanding of molecular genetics continues to grow, there remains a need to identify additional germline and somatic mutations and alterations that may increase an individual s risk to develop prostate cancer and potentially the aggressiveness of the disease. In studying the following alterations in prostate cancer, in both localized and advanced stages, potential expanded molecular findings may lead to actionable therapeutic targets and biomarker development. A better understanding of molecular genetics in a longitudinal study of subjects with prostate cancer may be helpful for the design of future treatment studies, and to develop a better understanding of the natural history of the disease Objectives: - To longitudinally evaluate subjects with prostate cancer with known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM to better understand the natural history of the disease. - To longitudinally evaluate subjects with tumor mutational burden-high (TMB-H) prostate cancer [greater than or equal to 10 mutations/megabase (mut/Mb)]. Eligibility: - Subjects with histologically confirmed prostate cancer - Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high or be deemed an exceptional responder. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified) - Age greater than or equal to 18 years old Design: - This will be a long-term multi-center study to comprehensively study participants with prostate cancer. - Participants will provide clinical information (including medical history, clinical tests, imaging studies and reports, surgical pathology reports, genetic test results). - Since long-term follow-up of individuals with prostate cancer is a major feature of the study, local sites intend to maintain active contact with study subjects for as long as possible. Participants will be followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies and duration of responses.

Estado general Not yet recruiting
Fecha de inicio January 19, 2021
Fecha de Terminación June 30, 2027
Fecha de finalización primaria June 30, 2026
Tipo de estudio Observational
Resultado primario
Medida Periodo de tiempo
natural history of prostate cancer with known germline and/or somatic variants ongoing
natural history of TMB-H prostate cancer ongoing
Inscripción 2000
Condición
Elegibilidad

Método de muestreo: Probability Sample

Criterios:

- INCLUSION CRITERIA: - Subjects with histologically confirmed prostate cancer. - Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, and/or MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high([defined as greater than or equal to 10 mutations/megabase (mut/Mb)]. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified) OR - be deemed an exceptional responder. NOTE: an exceptional response is defined as achievement of either a) a complete response, or b) a confirmed partial response in a trial or treatment or a response of exceptionally long duration - Age greater than or equal to 18 years old. - Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: -None

Género: Male

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
William L Dahut, M.D. Principal Investigator National Cancer Institute (NCI)
Contacto general

Apellido: Katherine O Lee-Wisdom, R.N.

Teléfono: (240) 858-3525

Email: [email protected]

Ubicación
Instalaciones: Contacto: National Institutes of Health Clinical Center For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 TTY8664111010 [email protected]
Ubicacion Paises

United States

Fecha de verificación

January 11, 2021

Fiesta responsable

Tipo: Sponsor

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Grupo de brazo

Etiqueta: Cohort 1

Descripción: Subjects with histologically confirmed prostate cancer and genomic testing results

Etiqueta: Cohort 2

Descripción: Subjects with histologically confirmed prostate cancer who deemed to be an exceptional responder with or without genomic testing results

Información de diseño del estudio

Modelo de observación: Cohort

Perspectiva de tiempo: Prospective

Fuente: ClinicalTrials.gov