EXPRESS: EXcePtional RESponSe - Exceptional and Unexpected Response to Targeted Therapies

Metastatic Cancers Clinical Trial

— EXPRESS  

Official title:

Low Level of Genomic Alteration to Predict Exceptional and Unexpected Response to Targeted Therapies in Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02701907
• Other study ID #: UC-0105/1508
• Secondary ID: 2015-A01500-49
• Status: Completed
• Phase: N/A
• Start date: December 2016
• Est. completion date: April 17, 2022

Study information

• Verified date: September 2022
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 182
• Est. completion date: April 17, 2022
• Est. primary completion date: April 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancers
• Neoplasm Metastasis

Intervention

Other:
• Blood sampling

Locations

Country	Name	City	State
France	Clinique de l'Europe	Amiens
France	CHU d'Angers	Angers
France	Institut de Cancérologie de l'Ouest (site Paul Papin)	Angers
France	Centre Hospitalier Annecy Genevois (CHANGE) - site d'Annecy	Annecy
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 Hospitalier Metropole Savoie	Chambéry
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	Hôpital Clinique Claude Bernard	Metz
France	Institut de Cancérologie de Lorraine	Nancy
France	Institut de Cancérologie de l'Ouest (site René Gauducheau)	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHR d'Orléans - Hôpital de la Source	Orléans
France	Curie Paris	Paris
France	Hôpital Européen Georges Pompidou (HEGP)	Paris
France	Hôpital Saint Louis	Paris
France	Centre Hospitalier Lyon Sud - Hospices Civils de Lyon	Pierre-Bénite
France	CHU de Poitiers - Pôle régional de Cancérologie	Poitiers
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

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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