Umístění molekulárních markerů v klinické rutině pro léčbu pacientů s rakovinou/nádory nadledvin (COMETE-CARE) (COMETE-CARE)
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 :
- 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.
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Secondary objective : to estimate the impact of COMETE biomarkers on patients management.
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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)
- Correlation of molecular markers with morphological features (radiological and pathological) of the tumor
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
- 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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Guillaume Assie, Pr
- Telefonní číslo: 01 58 41 18 20
- E-mail: guillaume.assie@aphp.fr
Studijní záloha kontaktů
- Jméno: Christelle AUGER, Chef de projet
- Telefonní číslo: 01 71 76 07 53
- E-mail: christelle.auger@aphp.fr
Studijní místa
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Paris, Francie, 75014
- Nábor
- GH Paris Centre, Assistance Publique - Hôpitaux de Paris
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Kontakt:
- Guillaume ASSIE, Pr
- Telefonní číslo: 01 58 41 18 20
- E-mail: guillaume.assie@aphp.fr
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Kontakt:
- Christelle AUGER, Chef de projet
- Telefonní číslo: 01 71 76 07 53
- E-mail: christelle.auger@aphp.fr
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria
- Patients 18 years of age and older
- Patients with an adrenal tumor who will be operated or have been operated in the last 2 months of a potentially malignant adrenocortical (ACC) (any tumor with density > 10 UH) 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)
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Diagnostický
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Jiný: Patients with ACC
These patients will be followed up and proposed a search for targetable molecular alterations |
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 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 For patients with ACC and patients with MPP : tumor sample during surgery |
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Jiný: Patients with MPP
These patients will be followed up and proposed a search for targetable molecular alterations |
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 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 For patients with ACC and patients with MPP : tumor sample during surgery |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Baseline biomarkers results
Časové okno: Within 3 months after surgery
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after initial surgery |
Within 3 months after surgery
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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M3 biomarkers results
Časové okno: During follow-up (month 6)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M6 follow-up visit |
During follow-up (month 6)
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M6 biomarkers results
Časové okno: During follow-up (month 9)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M9 follow-up visit |
During follow-up (month 9)
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M9 biomarkers results
Časové okno: During follow-up (month 12)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M12 follow-up visit |
During follow-up (month 12)
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M12 biomarkers results
Časové okno: During follow-up (month 15)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M15 follow-up visit |
During follow-up (month 15)
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M15 biomarkers results
Časové okno: During follow-up (month 18)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M18 follow-up visit |
During follow-up (month 18)
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M18 biomarkers results
Časové okno: During follow-up (month 21)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M21 follow-up visit |
During follow-up (month 21)
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M21 biomarkers results
Časové okno: During follow-up (month 24)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M24 follow-up visit |
During follow-up (month 24)
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M24 biomarkers results
Časové okno: During follow-up (month 27)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M27 follow-up visit |
During follow-up (month 27)
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M27 biomarkers results
Časové okno: During follow-up (month 30)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M30 follow-up visit |
During follow-up (month 30)
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M30 biomarkers results
Časové okno: During follow-up (month 33)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M33 follow-up visit |
During follow-up (month 33)
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M33 biomarkers results
Časové okno: During follow-up (month 36)
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Proportion of biomarkers and of informative biomarkers returned to physicians within 3 months after M36 follow-up visit |
During follow-up (month 36)
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: Anne JOUINOT, Dr, APHP
Publikace a užitečné odkazy
Obecné publikace
- 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.
- Lenders JWM, Kerstens MN, Amar L, Prejbisz A, Robledo M, Taieb D, Pacak K, Crona J, Zelinka T, Mannelli M, Deutschbein T, Timmers HJLM, Castinetti F, Dralle H, Widimsky J, Gimenez-Roqueplo AP, Eisenhofer G. Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020 Aug;38(8):1443-1456. doi: 10.1097/HJH.0000000000002438.
- Jouinot A, Lippert J, Sibony M, Violon F, Jeanpierre L, De Murat D, Armignacco R, Septier A, Perlemoine K, Letourneur F, Izac B, Ragazzon B, Leroy K, Pasmant E, North MO, Gaujoux S, Dousset B, Groussin L, Libe R, Terris B, Fassnacht M, Ronchi CL, Bertherat J, Assie G. Transcriptome in paraffin samples for the diagnosis and prognosis of adrenocortical carcinoma. Eur J Endocrinol. 2022 Apr 21;186(6):607-617. doi: 10.1530/EJE-21-1228.
- 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.
- Bancos I, Taylor AE, Chortis V, Sitch AJ, Jenkinson C, Davidge-Pitts CJ, Lang K, Tsagarakis S, Macech M, Riester A, Deutschbein T, Pupovac ID, Kienitz T, Prete A, Papathomas TG, Gilligan LC, Bancos C, Reimondo G, Haissaguerre M, Marina L, Grytaas MA, Sajwani A, Langton K, Ivison HE, Shackleton CHL, Erickson D, Asia M, Palimeri S, Kondracka A, Spyroglou A, Ronchi CL, Simunov B, Delivanis DA, Sutcliffe RP, Tsirou I, Bednarczuk T, Reincke M, Burger-Stritt S, Feelders RA, Canu L, Haak HR, Eisenhofer G, Dennedy MC, Ueland GA, Ivovic M, Tabarin A, Terzolo M, Quinkler M, Kastelan D, Fassnacht M, Beuschlein F, Ambroziak U, Vassiliadi DA, O'Reilly MW, Young WF Jr, Biehl M, Deeks JJ, Arlt W; ENSAT EURINE-ACT Investigators. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study. Lancet Diabetes Endocrinol. 2020 Sep;8(9):773-781. doi: 10.1016/S2213-8587(20)30218-7. Epub 2020 Jul 23.
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Dokončení studie (Odhadovaný)
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První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
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Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- APHP210350
- 2022-A00663-40 (Jiný identifikátor: ID-RCB Number)
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