Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Baseline biomarkers results
研究概览
简要总结
The adrenal cancer research network "COMETE" is federating French research on rare adrenal cancers. COMETE achieved major breakthroughs in the molecular characterization of adrenocortical carcinomas (ACC) and malignant pheochromocytomas/paragangliomas (MPP). Recently, COMETE successfully derived potential biomarkers for prognosis, theranostic and follow-up. Those biomarkers have been retrospectively validated. However the benefit for patients in real life conditions is not yet established.
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Main objective : to implement COMETE biomarkers as a routine standard of care for adrenal cancer.
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The primary end point is double :
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Proportion of biomarkers results provided within 3 months after surgery,
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The proportion of "informative" biomarkers, corresponding to markers passing quality controls and returning a value that is not in the grey zone of the measure.
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Secondary objective : to estimate the impact of COMETE biomarkers on patients management.
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Secondary endpoints :
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Proportion of patients with discrepant clinical and molecular markers ; for discrepancies, proportion of decisions impacted by biomarkers results
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Proportion of high risk patients for whom an actionable molecular target was identified
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Predictive value (positive and negative) of biomarkers to detect recurrences
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Molecular signatures of "extraordinary responders" to treatments (corresponding to the exceptional RECIST complete response, or to the >80% tumor reduction sutained for >6months)
详细描述
- Adult patients with a malignant adrenal tumor before initial surgery are proposed to participate to the study.
- Initial clinical management following current guidelines is applied, including clinical and morphological evaluation, hormone assays and adrenal surgery. A tumor sample from initial surgery , and a blood sample and a urine sample collected before surgery are included in the current research protocol. These samples are used to run prognostic molecular measurements, in order to classify patients as "low" or "high risk" of recurrence. For ACC samples, paraffin tumor samples will be sent to a centralized pathology facility, where 3' RNA sequencing will be performed on tumor RNA to classify tumors into previously established C1A/C1B prognostic classification. Circulating levels of miRNAs will be assayed from blood samples collected before surgery and used to classify tumors into prognostic categories as previously reported. Urine and plasma steroids profiles will be established using mass spectrometry to classify tumors into prognostic categories as previously reported. For MPP, molecular assays will include somatic genotyping, methylation assays and immunochemistry for the known recurrently altered genes, and used to classify tumors into prognostic categories as previously reported. These molecular results are returned by 3 months after surgery
- Patients follow-up is then performed following current guidelines, with repeated visits (each ~3 months for ACC and ~6 months for MPP), including clinical, morphological evaluation, and hormone assays. A blood and a urine sample will also be collected for the current research protocol. These samples will be used to run molecular measurements aiming at identifying early recurrence. For ACC, circulating levels of miRNAs and urine and plasma steroids profiles will be measured every 3 months to classify tumors into prognostic categories as previously reported. For MPP, circulating levels of miRNAs will be measured every 6 months to classify tumors into prognostic categories as previously reported
- For patients at high risk of recurrence, a molecular target will be searched by an extended genomic analysis of the tumor (exome sequencing and RNA sequencing), in search for molecular targets that may orient future treatments, if the disease recurs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Baseline biomarkers results
时间窗: Within 3 months after surgery
Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after initial surgery
次要结局
- M15 biomarkers results(During follow-up (month 18))
- M3 biomarkers results(During follow-up (month 6))
- M24 biomarkers results(During follow-up (month 27))
- M12 biomarkers results(During follow-up (month 15))
- M21 biomarkers results(During follow-up (month 24))
- M27 biomarkers results(During follow-up (month 30))
- M33 biomarkers results(During follow-up (month 36))
- M6 biomarkers results(During follow-up (month 9))
- M9 biomarkers results(During follow-up (month 12))
- M30 biomarkers results(During follow-up (month 33))
- M18 biomarkers results(During follow-up (month 21))