Clinical trial NCT02701907: EXPRESS: EXcePtional RESponSe - Exceptional and Unexpected Response to Targeted Therapies
Official title: Low Level of Genomic Alteration to Predict Exceptional and Unexpected Response to Targeted Therapies in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Cancers
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2016-03-08
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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)

Eligibility criteria: Inclusion Criteria:

1. Adult patient ( ≥18 years old at diagnosis).
2. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
3. 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.
4. Metastatic or locally advanced disease.
5. 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.
6. 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.
7. 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.
8. Availability of normal tissue along with the tumor tissue, otherwise blood sample in order to extract constitutional DNA.

Exclusion Criteria:

1. Pediatric patient (\<18 years old at diagnosis).
2. Hematological malignancy or solid tumors, which are not in the scope of tumor types described in the inclusion criteria.
3. Tumor sample not available or not reaching the required quality for whole exome sequencing analysis.
4. Absence of confirmation of the exceptional and unexpected pattern of response by the college of experts as defined above.

Primary outcomes:
measure: 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
timeFrame: 42 months
Secondary outcomes:
measure: The secondary endpoint is the rate of tumors with low level of genomic alterations between the EXPRESS cohort and control cohorts of patients.
timeFrame: 42 months
measure: 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
timeFrame: 42 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Clinique de l'Europe
city: Angers
country: France
facility: CHU d'Angers
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest (site Paul Papin)
city: Annecy
country: France
facility: Centre Hospitalier Annecy Genevois (CHANGE) - site d'Annecy
city: Auxerre
country: France
facility: CHU d'Auxerre
city: Avignon
country: France
facility: Institut Sainte-Catherine
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Chalon-sur-Saône
country: France
facility: Hôpital Privé Sainte Marie
city: Chambéry
country: France
facility: Centre Hospitalier Metropole Savoie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Corbeil
country: France
facility: CH Sud Francilien
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: Guilherand-Granges
country: France
facility: Hôpital Privé Drôme Ardèche - Clinique Pasteur
city: Lille
country: France
facility: Centre Oscar Lambret
city: Longjumeau
country: France
facility: CH de Longjumeau
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hôpital Nord
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Metz
country: France
facility: Hôpital Clinique Claude Bernard
city: Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest (site René Gauducheau)
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: CHR d'Orléans - Hôpital de la Source
city: Paris
country: France
facility: Curie Paris
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP)
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
city: Poitiers
country: France
facility: CHU de Poitiers - Pôle régional de Cancérologie
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Romans-sur-Isère
country: France
facility: Hôpitaux Drôme-Nord- Site de Romans sur Isère
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Charles Ferté, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: