Clinical trial NCT02672020: Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card
Official title: The COMETE Network, Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adrenal Gland Neoplasms
Keywords: pheochromocytoma
paraganglioma
adrenocortical carcinoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Institut National de la Santé Et de la Recherche Médicale, France
name: National Cancer Institute, France
First posted: 2016-02-03
Enrollment: 448
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care.

The main objective of COMETE-TACTIC is to provide an easy-to-use "identity card" of the adrenal tumors that will allow a personalized "à la carte" management of the patient and, when indicated, to the indication of the most accurate molecular targeted therapy.

We hypothesize that the improvement of MPP and ACC diagnosis and of the therapeutic options proposed to affected patients will require,

1. the transfer to routine practice and the prospective validation of the novel diagnostic and predictive biomarkers issued from recent discoveries (genetics, genomics, histological biomarkers);
2. the implementation of the translational research projects based on the COMETE collection to identify circulating diagnostic, prognostic and therapeutic genetic and metabolic biomarkers that could be used as non-invasive "liquid biopsies".

Detailed description: Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE ('COrtex, MEdulla Tumors Endocrines') network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. COMETE has published more than 200 papers and performed seminal work on the pathophysiology and the genetics of MPP and ACC published in high-impact journals.

This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care.

The main objective of COMETE-TACTIC program is to design and validate an easy-to-use "identity card" classifying MPP and ACC in clinical routine, using molecular genomic and metabolomic tools combined with histopathological-based tests, to provide a real help for early diagnosis, prognostic as well as a personalized "à la carte" management and treatment to patients with malignant adrenal tumors. Seven teams, with an expertise in genomics of adrenal tumors, or in metabolomics approaches, or in clinical research and statistical analyses collaborate in COMETE-TACTIC. COMETE-TACTIC will be based on an already constituted large cohort of 850 patients that will be enlarged by the prospective enrolment of new cases and biological samples (300 to 450 new cases during the 3 years of the project) via 21 French expert and/or competence centers of COMETE-Cancer Reference center.

Previous COMETE basic studies provided important new insight for the understanding of molecular mechanisms responsible for MPP or ACC. With the transfer of "Omics"-based tests from research laboratories to clinical practice, COMETE-TACTIC is the next step toward a personalized medicine for patients with MPP and ACC. COMETE-TACTIC should speed the transfer in routine clinical care of new biomarkers based on cutting-edge technologies combining advanced pathology assessment and targeted genomics and metabolomics to diagnose malignancy and predict outcome, and thereby facilitating a more accurate, rapid and reliable diagnostic work-up for patients. This personalized management will help to avoid delayed diagnosis and to direct clinical decisions resulting in a better health outcome for the patients. COMETE-TACTIC will offer the access to a precise molecular classification of MPP and ACC that should guide targeted therapies. Finally, COMETE-TACTIC will investigate for the first time the impact of circulating biomarkers for the diagnosis and prognostic of adrenal cancers that will be further tested as biomarkers of response to targeted therapies.

Eligibility criteria: Inclusion Criteria:

* Patient operated on a tumor developed from the adrenal cortex or a pheochromocytoma or a paraganglioma
* Age≥15 years
* Signature of the informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Malignant status
timeFrame: Up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU-Angers
city: Bois-Guillaume
country: France
facility: CHU Rouen-Hopital de Bois-Guillaume
city: Bordeaux
country: France
facility: CHU Bordeaux, Hopital du Haut Leveque
city: Brest
country: France
facility: CHU Brest, Hopital de la Cavale Blanche
city: Bron
country: France
facility: HCL- Centre Hospitalier Lyon Est
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand, Hopital Gabriel Montpied
city: Grenoble
country: France
facility: CHU Grenoble- Hopital Albert Michallon
city: Le Kremlin Bicetre
country: France
facility: Assistance Publique Hopitaux de Pais, Hopital de Bicetre
city: Limoges
country: France
facility: CHU Limoges, Hopital du Cluzeau
city: Montpellier
country: France
facility: CHU Montpellier, Hopital Lapeyronie
city: Nantes
country: France
facility: CHU Nantes, Hopital Laënnec
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris -HEGP
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris, Cochin
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris, Necker
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris, Pitie Salpetriere
city: Reims
country: France
facility: CHU Reims, Hopital Robert Debre
city: Rennes
country: France
facility: CHU Rennes, Hopital Sud
city: Strasbourg
country: France
facility: CHU Strasbourg, Hopital de Hautepierre
city: Toulouse
country: France
facility: CHU Toulouse, IUC Oncopole
city: Tours
country: France
facility: CHU Tours, Hopital Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Assistance Publique Hopitaux de Paris-HEGP, Paris, France
name: Anne-Paule GIMENEZ-ROQUEPLO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Castro-Vega LJ, Letouze E, Burnichon N, Buffet A, Disderot PH, Khalifa E, Loriot C, Elarouci N, Morin A, Menara M, Lepoutre-Lussey C, Badoual C, Sibony M, Dousset B, Libe R, Zinzindohoue F, Plouin PF, Bertherat J, Amar L, de Reynies A, Favier J, Gimenez-Roqueplo AP. Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas. Nat Commun. 2015 Jan 27;6:6044. doi: 10.1038/ncomms7044.
citation: Letouze E, Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, Janin M, Menara M, Nguyen AT, Benit P, Buffet A, Marcaillou C, Bertherat J, Amar L, Rustin P, De Reynies A, Gimenez-Roqueplo AP, Favier J. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell. 2013 Jun 10;23(6):739-52. doi: 10.1016/j.ccr.2013.04.018. Epub 2013 May 23.
citation: Assie G, Letouze E, Fassnacht M, Jouinot A, Luscap W, Barreau O, Omeiri H, Rodriguez S, Perlemoine K, Rene-Corail F, Elarouci N, Sbiera S, Kroiss M, Allolio B, Waldmann J, Quinkler M, Mannelli M, Mantero F, Papathomas T, De Krijger R, Tabarin A, Kerlan V, Baudin E, Tissier F, Dousset B, Groussin L, Amar L, Clauser E, Bertagna X, Ragazzon B, Beuschlein F, Libe R, de Reynies A, Bertherat J. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014 Jun;46(6):607-12. doi: 10.1038/ng.2953. Epub 2014 Apr 20.