Clinical trial NCT05754892: Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)
Official title: Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cancer
Adrenal
Keywords: biological markers
genomics
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2023-03-06
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Baseline biomarkers results
timeFrame: Within 3 months after surgery
Secondary outcomes:
measure: M3 biomarkers results
timeFrame: During follow-up (month 6)
measure: M6 biomarkers results
timeFrame: During follow-up (month 9)
measure: M9 biomarkers results
timeFrame: During follow-up (month 12)
measure: M12 biomarkers results
timeFrame: During follow-up (month 15)
measure: M15 biomarkers results
timeFrame: During follow-up (month 18)
measure: M18 biomarkers results
timeFrame: During follow-up (month 21)
measure: M21 biomarkers results
timeFrame: During follow-up (month 24)
measure: M24 biomarkers results
timeFrame: During follow-up (month 27)
measure: M27 biomarkers results
timeFrame: During follow-up (month 30)
measure: M30 biomarkers results
timeFrame: During follow-up (month 33)
measure: M33 biomarkers results
timeFrame: During follow-up (month 36)
Other outcomes:
Locations:
city: Paris
country: France
facility: GH Paris Centre, Assistance Publique - Hôpitaux de Paris
Study officials:
affiliation: APHP
name: Anne JOUINOT, Dr
role: STUDY_DIRECTOR
References:
citation: Assie G, Jouinot A, Fassnacht M, Libe R, Garinet S, Jacob L, Hamzaoui N, Neou M, Sakat J, de La Villeon B, Perlemoine K, Ragazzon B, Sibony M, Tissier F, Gaujoux S, Dousset B, Sbiera S, Ronchi CL, Kroiss M, Korpershoek E, De Krijger R, Waldmann J, Quinkler M, Haissaguerre M, Tabarin A, Chabre O, Luconi M, Mannelli M, Groussin L, Bertagna X, Baudin E, Amar L, Coste J, Beuschlein F, Bertherat J. Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma. JAMA Oncol. 2019 Oct 1;5(10):1440-1447. doi: 10.1001/jamaoncol.2019.1558.
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citation: Chabre O, Libe R, Assie G, Barreau O, Bertherat J, Bertagna X, Feige JJ, Cherradi N. Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients. Endocr Relat Cancer. 2013 Jul 5;20(4):579-94. doi: 10.1530/ERC-13-0051. Print 2013 Aug.
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