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

Not Applicable

Recruiting

• Conditions: Cancer; Adrenal
• Interventions: Other: Blood sample; Other: Urine sample; Other: Tumor sample

• Registration Number: NCT05754892
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

* 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.

Study Timeline

• Study First Submitted: 2022-12-26
• Study First Submitted QC: 2023-02-22
• Study First Posted: 2023-03-06
• Study Start: 2023-10-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-09
• Primary Completion: 2029-12
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with ACC	Tumor sample	These patients will be followed up and proposed a search for targetable molecular alterations
Patients with MPP	Urine sample	These patients will be followed up and proposed a search for targetable molecular alterations
Patients with ACC	Urine sample	These patients will be followed up and proposed a search for targetable molecular alterations
Patients with MPP	Blood sample	These patients will be followed up and proposed a search for targetable molecular alterations
Patients with ACC	Blood sample	These patients will be followed up and proposed a search for targetable molecular alterations
Patients with MPP	Tumor sample	These patients will be followed up and proposed a search for targetable molecular alterations

Primary Outcome Measures

Name	Time	Method
Baseline biomarkers results	Within 3 months after surgery	Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after initial surgery

Secondary Outcome Measures

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

Trial Locations

Locations (1)

GH Paris Centre, Assistance Publique - Hôpitaux de Paris; 🇫🇷 Paris, France