EXPRESS: EXcePtional RESponSe - Exceptional and Unexpected Response to Targeted Therapies
- Conditions
- Metastatic Cancers
- Interventions
- Other: Blood sampling
- Registration Number
- NCT02701907
- Lead Sponsor
- UNICANCER
- Brief Summary
Adult patients with metastatic or locally advanced solid malignancies (including but not limited to breast, cancer, lung adenocarcinoma or squamous cell carcinoma, colorectal cancer, ovarian cancer, renal clear cell cancer, skin cutaneous melanoma), presenting or having presented an exceptional and unexpected response to an antineoplastic targeted therapy.
- Detailed Description
The primary endpoint is the rate of patients with tumors harboring a low level of genomic alteration (mutation, amplification or deletion) in genes (i.e. mutation, amplification, deletion) identified as causally implicated in cancer. A low level of genomic alteration is defined by the presence of less than the 5th quantile of genomic alterations to be expected in the given tumor type. Conversely, a high level of genomic alteration is defined by the presence of more than the 5th quantile of genomic alterations to be expected in the given tumor type.
The list of genes for which alterations are identified as causally implicated in cancer is defined by the Cancer Gene Census. This is an ongoing effort to catalogue those genes for which mutations, amplifications or deletions have been causally implicated in cancer. It is constantly updated by the Wellcome Trust Sanger Institute (UK) and available at: http://cancer.sanger.ac.uk/census (n=571 genes in September 2015)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 182
- Adult patient ( ≥18 years old at diagnosis).
- Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
- Patient suffering from the following tumor type: breast cancer, lung adenocarcinoma or squamous cell carcinoma, colorectal cancer, ovarian cancer, renal clear cell cancer, skin cutaneous melanoma.
- Metastatic or locally advanced disease.
- Currently or previously treated with an anticancer targeted therapy in monotherapy. Targeted therapies combined with other agents are accepted only if 1/ the tumor was previously proven to be progressive under the same agents or 2/ the response or the stability has been maintained with the targeted therapy alone after the agent has been stopped.
- Exceptional and unexpected tumor response to any marketed targeted therapy confirmed by the college of experts and defined as: complete response or partial response lasting more than six months, and not expected in more than 10% of the patients in this drug organ situation.
- Availability and required quality of the tumor biopsy (FFPE or frozen sample) allowing for the whole exome sequencing analysis. Tumor biopsies obtained just before the initiation of the targeted therapy are preferred; otherwise any prior sample is possible.
- Availability of normal tissue along with the tumor tissue, otherwise blood sample in order to extract constitutional DNA.
- Pediatric patient (<18 years old at diagnosis).
- Hematological malignancy or solid tumors, which are not in the scope of tumor types described in the inclusion criteria.
- Tumor sample not available or not reaching the required quality for whole exome sequencing analysis.
- Absence of confirmation of the exceptional and unexpected pattern of response by the college of experts as defined above.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description skin cutaneous melanoma Blood sampling In this study, the investigators aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. the investigators will focus analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed non-small cell lung cancer Blood sampling In this study, the investigators aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. The investigators will focus analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed kidney cancer Blood sampling In this study, the investigators aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. the investigators will focus analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed breast cancer Blood sampling In this study, we aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. We will focus our analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed ovarian cancer Blood sampling In this study, the investigators aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. the investigators will focus analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed colorectal cancer Blood sampling In this study, the investigators aim to assess whether tumors characterized by a low level of genomic alterations (mutation, amplification or deletion) are associated with unexpected and exceptional responses across targeted anticancer therapies. the investigators will focus analyses on tumor types for which molecular targeted anticancer agents are frequently prescribed
- Primary Outcome Measures
Name Time Method The primary endpoint is the rate of patients with tumors harboring a low level of genomic alteration (mutation, amplification or deletion) in genes (i.e. mutation, amplification, deletion) identified as causally implicated in cancer 42 months
- Secondary Outcome Measures
Name Time Method Exploratory analyses will be performed to compare the profiles between the EXPRESS and the control cohorts of patients, to identify novel candidate somatic molecular profiles 42 months The secondary endpoint is the rate of tumors with low level of genomic alterations between the EXPRESS cohort and control cohorts of patients. 42 months
Trial Locations
- Locations (36)
CHU d'Angers
🇫🇷Angers, France
Institut de Cancérologie de l'Ouest (site Paul Papin)
🇫🇷Angers, France
CHU d'Auxerre
🇫🇷Auxerre, France
Institut Sainte-Catherine
🇫🇷Avignon, France
Centre Hospitalier de la Côte Basque
🇫🇷Bayonne, France
Institut Bergonié
🇫🇷Bordeaux, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
Hôpital Privé Sainte Marie
🇫🇷Chalon-sur-Saône, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
CH Sud Francilien
🇫🇷Corbeil, France
Centre Georges-François Leclerc
🇫🇷Dijon, France
Hôpital Privé Drôme Ardèche - Clinique Pasteur
🇫🇷Guilherand-Granges, France
Centre Oscar Lambret
🇫🇷Lille, France
CH de Longjumeau
🇫🇷Longjumeau, France
Centre Léon Bérard
🇫🇷Lyon, France
Hôpital Privé Jean Mermoz
🇫🇷Lyon, France
Hôpital Nord
🇫🇷Marseille, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Institut de Cancérologie de Lorraine
🇫🇷Nancy, France
Hôpital Clinique Claude Bernard
🇫🇷Metz, France
Centre Antoine Lacassagne
🇫🇷Nice, France
CHR d'Orléans - Hôpital de la Source
🇫🇷Orléans, France
Hôpital Européen Georges Pompidou (HEGP)
🇫🇷Paris, France
Curie Paris
🇫🇷Paris, France
Hôpital Saint Louis
🇫🇷Paris, France
CHU de Poitiers - Pôle régional de Cancérologie
🇫🇷Poitiers, France
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
🇫🇷Pierre-Bénite, France
Centre Eugène Marquis
🇫🇷Rennes, France
Hôpitaux Drôme-Nord- Site de Romans sur Isère
🇫🇷Romans-sur-Isère, France
Institut de Cancérologie de la Loire
🇫🇷Saint Priest en Jarez, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Gustave Roussy
🇫🇷Villejuif, France
Clinique de l'Europe
🇫🇷Amiens, France
Centre Hospitalier Annecy Genevois (CHANGE) - site d'Annecy
🇫🇷Annecy, France
Institut de Cancérologie de l'Ouest (site René Gauducheau)
🇫🇷Nantes, France
Centre Hospitalier Metropole Savoie
🇫🇷Chambéry, France