Pre-therapeutic Identification of Dihydropyrimidine Dehydrogenase Gene (DPD) Deficiency for Predicting Toxicity to Fluoropyrimidines (DPD côlon)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01547923|
Recruitment Status : Unknown
Verified March 2012 by ICO Paul Papin.
Recruitment status was: Recruiting
First Posted : March 8, 2012
Last Update Posted : March 8, 2012
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Intravenous 5 Fluorouracile||Genetic: Blood sample for phenotypic and pharmacogenetic analysis.||Phase 3|
The fluoropyrimidines, of which 5-Fluorouracil is the most important, represent a family of medication that is used in particular in cancerology. They are molecules widely used in cancerology since they can be found in nearly 45% of chemotherapy protocols and in the treatment of about 50% of cancers (colorectum, oesophagus, stomach, breast, upper digestive and respiratory tracts). They are not only used in metastatic situations but also more and more in adjuvant situations, in other words for patients treated for a localised tumour, presenting a risk of relapse. A severe toxic risk cannot be tolerated in these conditions, and the doctor should assure the maximum level of safety for his patients. These medicines are the cause of 3% of grade IV toxicity from the first or second administration, and for 0.3% of deaths. To this one can add on a total of 20 to 25% grade III-IV toxic events.
Anticancer treatment is mostly administered by body size and in the best of cases after a few basic biological examinations such as a haemogram and renal status, without taking into consideration any individual particularities, whether genetic or epigenetic. Among potential toxicity risk factors one can find individual metabolic differences linked to genetic modifications of metabolism enzymes as well as differences in the chemical receptors and transporters.
For fluoropyrimidines, a polymorphism was found for the dihydropyrimidine dehydrogenase gene (DPD), a major catabolism enzyme. A deficit of this enzyme is a major counter-indication for the use of these medicines.
Early determination of DPD status would allow identification of patients at risk and would thus help in subsequent dose adjustment or selection of other treatment modalities.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2296 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Medical-financial Evaluation of Pre-therapeutic Screening by a Joint Phenotypic-pharmacogenetic Approach for Metabolic Fluoropyrimidine Enzyme Deficiency in Terms of Serious Toxicity Risk Prevention : a Multicentric Case Study|
|Study Start Date :||June 2008|
|Estimated Primary Completion Date :||December 2012|
|Estimated Study Completion Date :||December 2012|
Experimental: A : pre-therapeutic screening for DPD deficiency
Prior to treatment by fluoropyrimidines,a DPD deficiency is identified by a joint phenotypic-pharmacogenetic approach.
Genetic: Blood sample for phenotypic and pharmacogenetic analysis.
Prior to treatment by 5-FU, a DPD deficiency is identified thanks to just one blood sample (lithium heparinate).
B : no pretherapeutic research of DPD deficiency
For patients included in this arm, a blood sample will be taken prior to treatment by fluoropyrimidines but not analysed. If grade 3 or 4 toxicity levels are encountered during treatment, DPD deficiency will be detected.
Genetic: Blood sample for phenotypic and pharmacogenetic analysis.
Blood sample (lithium heparinate) will be taken prior to treatment but not analysed.
- Number and nature of grade IV toxicity. [ Time Frame: Up to 4 weeks. ]The percentage of severe toxicity (grade IV) will be analyzed in each arm. We expect a reduction of the early, severe, grade IV acute side-effects from 3% to 0.6% in the detected group with adapted doses.
- Number of grade III-IV toxic events. [ Time Frame: Up to 6 months. ]We expect a reduction of the number of grade III-IV toxic events, whenever they occur, from 25% to 5% in the detected group with adapted doses.
- Mortality rate. [ Time Frame: up to 6 months. ]The current mortality rate of 3 per thousand patients will be cut to 0 in the detected group with adapted doses.
- Medical-financial study of pre-therapeutic screening. [ Time Frame: Up to 6 months. ]We will carry out a comparison of the prevention costs and the costs related to treating patients with toxicity. Direct costs and indirect costs will be taken into account.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01547923
|Contact: Virginie Berger, MD, PhD||33 2 41 35 27 firstname.lastname@example.org|
|Contact: Jessy Delaye, M Sc||33 2 41 35 29 email@example.com|
|ICO Paul Papin||Recruiting|
|Angers, France, 49933|
|Contact: Olivier Capitain, MD, PhD firstname.lastname@example.org|
|Principal Investigator: Olivier Capitain, MD, PhD|
|CHU Jean Minjoz||Recruiting|
|Besançon, France, 25000|
|Contact: Christophe Borg, MD email@example.com|
|Principal Investigator: Christophe Borg, MD|
|CHU Morvan||Not yet recruiting|
|Brest, France, 29609|
|Contact: Hélène Simon, MD firstname.lastname@example.org|
|Principal Investigator: Hélène Simon, MD|
|CHU Côte de Nacre||Recruiting|
|Caen, France, 14033|
|Contact: Karine Bouhier Leporrier, MD email@example.com|
|Principal Investigator: Karine Bouhier Leporrier, MD|
|Centre François Baclesse||Recruiting|
|Caen, France, 14076|
|Contact: Marie-Pierre Galais, MD firstname.lastname@example.org|
|Principal Investigator: Marie-Pierre Galais, MD|
|Pôle Santé Léonard de Vinci||Recruiting|
|Chambray-les-Tours, France, 37175|
|Contact: Pierre-Etienne Cailleux, MD email@example.com|
|Principal Investigator: Pierre-Etienne Cailleux, MD|
|Centre Hospitalier du Haut Anjou||Recruiting|
|Chateau-Gontier, France, 53204|
|Contact: Valérie Rossi, MD firstname.lastname@example.org|
|Principal Investigator: Valérie Rossi, MD|
|Cholet, France, 49325|
|Contact: Medhi Kaassis, MD email@example.com|
|Principal Investigator: Medhi Kaassis, MD|
|Clinique des Cèdres||Not yet recruiting|
|Cornebarrieu, France, 31700|
|Contact: Isabelle Roque, MD firstname.lastname@example.org|
|Principal Investigator: Isabelle Roque, MD|
|Hôpital Henri Mondor||Recruiting|
|Créteil, France, 94010|
|Contact: Isabelle Baumgaertner, MD email@example.com|
|Principal Investigator: Isabelle Baumgaertner, MD|
|CH Sarthe et Loir||Recruiting|
|La Flèche, France, 72205|
|Contact: Ludovic Rosenfeld, MD firstname.lastname@example.org|
|Principal Investigator: Ludovic Rosenfeld, MD|
|Centre Hospitalier Les oudairies||Recruiting|
|La Roche Sur Yon, France, 85929|
|Contact: Roger Faroux, MD email@example.com|
|Principal Investigator: Roger Faroux, MD|
|Laval, France, 53015|
|Contact: Claire Stampfli, MD firstname.lastname@example.org|
|Principal Investigator: Claire Stampfli, MD|
|Le Mans, France, 72037|
|Contact: Oana Cojocarasu, MD email@example.com|
|Principal Investigator: Oana Cojocarasu, MD|
|Centre Oscar Lambret||Recruiting|
|Lille, France, 53020|
|Contact: Eric Amela, MD firstname.lastname@example.org|
|Principal Investigator: Eric Amela, MD|
|Centre d'oncologie de Gentilly||Recruiting|
|Nancy, France, 54100|
|Contact: Célia Roemer-Becuwe, MD email@example.com|
|Principal Investigator: Celia Roemer Becuwe, MD|
|CHU Hotel Dieu||Recruiting|
|Nantes, France, 44093|
|Contact: Tamara Matysiak, MD firstname.lastname@example.org|
|Principal Investigator: Tamara Matysiak Budnik, MD|
|Centre Antoine Lacassagne||Recruiting|
|Nice, France, 06189|
|Contact: Eric François, MD email@example.com|
|Principal Investigator: Eric François, MD|
|HEGP||Not yet recruiting|
|Paris, France, 75015|
|Contact: Julien Taieb, MD firstname.lastname@example.org|
|Principal Investigator: Julien Taieb, MD|
|Centre Hospitalier Lyon Sud||Recruiting|
|Pierre Bénite, France, 69495|
|Contact: Cécile Fournel-Federico, MD email@example.com|
|Principal Investigator: Cécile Fournel Federico, MD|
|Saumur, France, 49403|
|Contact: Véronique Guérin-Meyer, MD firstname.lastname@example.org|
|Principal Investigator: Véronique Guérin-Meyer, MD|
|ICO René Gauducheau||Recruiting|
|St Herblain, France, 44805|
|Contact: Jaafar Bennouna, MD email@example.com|
|Principal Investigator: Jaafar Bennouna, MD|
|Institut Claudius Regaud||Recruiting|
|Toulouse, France, 31052|
|Contact: Jean-Pierre Delord, MD firstname.lastname@example.org|
|Principal Investigator: Jean-Pierre Delord, MD|
|Toulouse, France, 31059|
|Contact: Corinne Couteau, MD email@example.com|
|Principal Investigator: Corinne Couteau, MD|
|Tours, France, 37044|
|Contact: Thierry Lecomte, MD firstname.lastname@example.org|
|Principal Investigator: Thierry Lecomte, MD|
|Principal Investigator:||Olivier Capitain, MD, PhD||ICO Paul Papin|