Phase I Trials Platform in Oncology, CITOHL

Skills - Research

Phase 1 clinical Trial Design

In collaboration with EMR 3738 laboratory involved in pharmacometrics and modeling at Lyon-Sud Medicine University, the academic physicians and searchers of the Plateform can design traditional 3 + 3 phase I trials or more sophisticated phase I-II trials including model-based escalation design (i.e. CRM…), pharmacokinetically-guided or PK-PD modelling-based dose adjustments. They have developed a particular interest in identification of the optimal dose and dosing schedule of study drugs given as single agents or in combinations using PK-PD-PG modeling.

Phase 1 clinical Trial Conduction

The staffs of phase I trial Plateform are skilled to perform phase I and phase II trials in medical oncology. Some of them were trained with international teams recognized for early phase clinical trials in North America.

The Plateform has successfully conducted several academic or industry-sponsored phase I and II studies which were published in international peer-reviewed journals (See Publications). Several audits validated its high level activities in clinical trial conduction and monitoring. As a result, it was certified as one of the 14 early phase trial centers by the French NCI in November 2010.

Modelling

The internationally renowned expertise of the laboratory offers two complementary areas of skill: the clinical pharmacology of the antineoplastic agents and population pharmacokinetic-pharmacodynamic (PK-PD) modelling: phenomenologic or mechanistic. This involves processing continuous or categorical data and is managed by Pr Michel Tod pharmacist as well as two biomathematicians Dr Emilie Henin and Olivier Colomban.

Experienced in PK-PD and PB-PK models, in mapping techniques and Bayesian approaches aimed at optimising dosage regimen, Michel Tod has developed different software, all of these fields.

Specialised in modelling PK-PD and biomarkers, Olivier Colomban is interested in the evaluation of therapeutic by biomarkers analysis and computeur management.


Analytical

Good quality results of the drug assays and those of their metabolites, is essential when later determining their pharmacokinetics or their bioequivalence. This quality is also assured by a quality control programme introduced within the biochemistry laboratory at the South Lyon Hospital. Antineoplastic agent assays are performed under the supervision of Pr Jérôme Guitton, in agreement with Good Laboratory Practice and GBEA (a guide to performing good analyses) to assure quality and transparency of all analytical operations. Three essential principles are respected: written procedures, quality control and filing.

Skills in the fields of analytical chemistry and pharmacology are necessary when compiling drug assay techniques. Within the EMR 3738 team, Professor Jérôme Guitton ensures the development and validation of the assays for drugs included in our studies, notably for assays achieved by liquid chromatography tandem mass spectrometry (LC-MS/MS). To date, many drugs are assayed by LC-MS/MS, including 5-fluorouracil, epirubicin, etoposide, irinotecan, vinorelbine and docetaxel. This infrastructure offers the possibility to assay new targeted agents (tyrosine kinase inhibitors, antibodies, etc…) with respect to the methods available.

Research Promoting

The team has been part of many organisation and scientific committees of scientific events and instigated many diverse seminars including:

  • Workshop: First European Course on Pharmacokinetics and Pharmacodynamics of Protein Therapeutics - Principles and Pharmacometric Approaches, Lausanne, Switzerland, 21-23 March 2016
  • Workshop: Mathematical modeling: a powerful tool for anticancer drug development, Lyon, France, 12th April 2012
  • NONMEM VI Intermediate Workshop, Marseille, France, April 2007
  • Workshop on Cancer Modelling and Therapeutic Innovation: From Theory to Clinic, Lyon, France, 26th and 27th September 2006
  • Workshop: Optimal Population PK design & Bootstrap, randomization and mixture model tests in NONMEM, Marseille, France, 10th and 11th October 2004
  • Symposium: New Algorithm Development in the Field of Non-Linear Mixed Effect Model, Lyon, France, 13 September 2004
  • NONMEM basic and intermediate Workshop, Lyon. Avec Stuart Beal et Lewis Sheiner: 1991, 93, 97, 2001.