Evaluation of Somatic Mutation Spectrum as Biomarker for Survival Outcome in Chinese CRC
14 de enero de 2020 actualizado por: Ruihua Xu, Sun Yat-sen University
A Cohort Study Evaluating the Effectiveness of the Somatic Mutation Spectrum Model in CRC Prognosis and Prediction Stratification
By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.
Descripción general del estudio
Estado
Desconocido
Condiciones
Descripción detallada
Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC.
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.
Tipo de estudio
De observación
Inscripción (Anticipado)
1500
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Guangdong
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Guangzhou, Guangdong, Porcelana, 510060
- Reclutamiento
- Medical Oncology,Sun Yat-sen University Cancer Center
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Contacto:
- Feng Wang, M.D,Ph.D
- Correo electrónico: wangfeng@sysucc.org.cn
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria.
In addition, the patient of the prospective cohort should be thoroughly informed about the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent.
The written informed consent of the prospective cohort should be obtained from the patient prior to enrollment.
The following criteria apply to all patients enrolled onto the study unless otherwise specified.
Descripción
Inclusion Criteria:
Retrospective cohort:
- The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.
- The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.
- The clinical data of patients are complete.
- The treatment record of the patients after surgery are complete, and the fellow-up data are available.
Prospective cohort:
- Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.
- Paired 10 ml blood and tissue samples should be available
- The clinical informations of patients and definite pathological diagnosis of colorectal cancer should be obtained
- Patients agree with the group to follow-up them and provide follow-up informations
- Performance status ECOG（Eastern Cooperative Oncology Group） score ≤2
- Informed consent must be obtained from the patient
Exclusion Criteria:
Retrospective cohort:
- The patient had previous history of tumor prior to colorectal cancer surgery
- The clinical data of patients are not available
4. The date of treatment after surgery are not integrity, outcome data are not available
Prospective cohort:
- The patient received a blood transfusion within three months;
- The patient has active HIV, hepatitis B or hepatitis C infection;
- pregnant patients;
- Alcohol or drug users;
- Other situation that researchers considered might affect the results of the experiment or violate the ethics.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Retrospective cohort
Whole exome sequencing of 2500 retrospective tissue sample.
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Prospective cohort
Whole exome sequencing of 500 prospectively collected tissue samples.
Panel sequencing of 451 genes of prospectively collected blood samples.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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prediction accuracy of survival rate
Periodo de tiempo: through study completion, an average of 5 years
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We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 5 year survival rate of patients is the primary endpoint
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through study completion, an average of 5 years
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prediction accuracy of recurrent rate
Periodo de tiempo: through study completion, an average of 3 years
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We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 3 year recurrent rate of patients is the primary endpoint
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through study completion, an average of 3 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Mutation Consistency of tissue and blood sample
Periodo de tiempo: through study completion, an average of 3 years
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We do NGS sequencing of both the tissue sample and blood sample of the CRC patients.
The gene mutation data will be analysis, and the percentage of same and different mutation of tissue and blood sample will be reported.
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through study completion, an average of 3 years
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Ruihua Xu, MD.,PhD, Sun Yat-sen University
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. Epub 2014 Apr 6.
- Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
- Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.
- Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
- Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, Zwaenepoel K, Gil-Bazo I, Passiglia F, Carreca AP, Taverna S, Vento R, Santini D, Peeters M, Russo A, Pauwels P. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim Biophys Acta. 2014 Dec;1846(2):539-46. doi: 10.1016/j.bbcan.2014.10.001. Epub 2014 Oct 16. Erratum In: Biochim Biophys Acta. 2015 Jan; 1855(1):17. Santini, Daniele [added].
- Yu SC, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de mayo de 2018
Finalización primaria (Anticipado)
1 de febrero de 2020
Finalización del estudio (Anticipado)
1 de mayo de 2021
Fechas de registro del estudio
Enviado por primera vez
28 de octubre de 2019
Primero enviado que cumplió con los criterios de control de calidad
11 de enero de 2020
Publicado por primera vez (Actual)
14 de enero de 2020
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
18 de enero de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
14 de enero de 2020
Última verificación
1 de enero de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- mutation spectrum model-CRC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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