Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)

Study Overview
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Brief Summary
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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. Main objective : to implement COMETE biomarkers as a routine standard of care for adrenal cancer. The primary end point is double : Proportion of biomarkers results provided within 3 months after surgery, 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. Secondary objective : to estimate the impact of COMETE biomarkers on patients management. Secondary endpoints : Proportion of patients with discrepant clinical and molecular markers ; for discrepancies, proportion of decisions impacted by biomarkers results Proportion of high risk patients for whom an actionable molecular target was identified Predictive value (positive and negative) of biomarkers to detect recurrences Molecular signatures of extraordinary responders to treatments (corresponding to the exceptional RECIST complete response, or to the >80% tumor reduction sutained for >6months)

Detailed Description
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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.

Official Title
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Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)

Conditions
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Cancer, Adrenal

Intervention / Treatment
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* Other: Blood sample
* Other: Urine sample
* Other: Tumor sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients 18 years of age and older Patients with an adrenal tumor who will be operated of a potentially malignant adrenocortical carcinoma (ACC) or pheochromocytoma or paraganglioma (MPP) (any stage, any secretion) Patients affiliated with a social security regime Patients who have signed an informed consent Exclusion Criteria Vulnerable populations : minors, pregnant or breastfeeding women, protected adults Patients on AME (state medical aid)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients with ACC<br>These patients will be followed up and proposed a search for targetable molecular alterations | Other: Blood sample<br>* For patients with ACC : blood (30ml) sampling before surgery and every 3 months during 3 years after surgery for biobanking For patients with MPP : blood (30ml) sampling before surgery and every 6 to 12 months for MPP during 3 years after surgery for biobanking<br>Other: Urine sample<br>* For patients with ACC : urine sampling before surgery and every 3 months during 3 years after surgery for biobanking For patients with MPP : urine sampling before surgery and every 6 to 12 months for MPP during 3 years after surgery for biobanking<br>Other: Tumor sample<br>* For patients with ACC and patients with MPP : tumor sample during surgery<br>|
| Other: Patients with MPP<br>These patients will be followed up and proposed a search for targetable molecular alterations | Other: Blood sample<br>* For patients with ACC : blood (30ml) sampling before surgery and every 3 months during 3 years after surgery for biobanking For patients with MPP : blood (30ml) sampling before surgery and every 6 to 12 months for MPP during 3 years after surgery for biobanking<br>Other: Urine sample<br>* For patients with ACC : urine sampling before surgery and every 3 months during 3 years after surgery for biobanking For patients with MPP : urine sampling before surgery and every 6 to 12 months for MPP during 3 years after surgery for biobanking<br>Other: Tumor sample<br>* For patients with ACC and patients with MPP : tumor sample during surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after initial surgery | Within 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| M3 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M6 follow-up visit | During follow-up (month 6) | 
| M6 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M9 follow-up visit | During follow-up (month 9) | 
| M9 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M12 follow-up visit | During follow-up (month 12) | 
| M12 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M15 follow-up visit | During follow-up (month 15) | 
| M15 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M18 follow-up visit | During follow-up (month 18) | 
| M18 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M21 follow-up visit | During follow-up (month 21) | 
| M21 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M24 follow-up visit | During follow-up (month 24) | 
| M24 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M27 follow-up visit | During follow-up (month 27) | 
| M27 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M30 follow-up visit | During follow-up (month 30) | 
| M30 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M33 follow-up visit | During follow-up (month 33) | 
| M33 biomarkers results | Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M36 follow-up visit | During follow-up (month 36) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biological markers, genomics