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

Cancer Clinical Trial

— COMETE-CARE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754892
• Other study ID #: APHP210350
• Secondary ID: 2022-A00663-40
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: June 2030

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Guillaume Assie, Pr
• Phone: 01 58 41 18 20
• Email: guillaume.assie[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: June 2030
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adrenal Gland Neoplasms
• Cancer

Intervention

Other:
• Blood sample
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
• Urine sample
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
• Tumor sample
For patients with ACC and patients with MPP : tumor sample during surgery

Locations

Country	Name	City	State
France	GH Paris Centre, Assistance Publique - Hôpitaux de Paris	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	National Cancer Institute, France

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)