Phase I Trials Platform in Oncology, CITOHL

Structure of the Platform - Activities in Clinical and Fundamental Research

Medical Oncology Department

The CITOHL is part of the Medical Oncology Department headed by Pr. V. Trillet-Lenoir at Lyon-Sud University Hospital (Hospices Civils de Lyon). This general medical oncology department is involved in treatment of patients with all types of cancer including gastro-intestinal, gynaecological, breast, urological and head and neck tumors. Ten full time medical oncologists, 1 general practitioner, 2 fellows and 3 oncology residents lead the medical activity in collaboration with 3 full time clinical research associate and 1 nurse.

Team involved in Early Phase Clinical Trials

It is composed of 4 full-time academic physicians (Pr. V. Trillet-Lenoir; Pr. Gilles Freyer; Dr Benoît You & Dr Julien Péron), 1 fellow, 3 full time clinical research associate and 1 nurse. About 50 patients a year with different types of cancers referred by all departments of Hospices Civils de Lyon are eligible to early phase clinical trials. Twelve in-patient hospitalization beds of the Medical Oncology and Haematology departments are dedicated to oncology and haematology clinical trials.

Technical Capacity of CITOHL

As part of the federation of oncohaematology, the team has access to full-time, as well as day-hospital beds, medical/surgical instrumentation, the intensive care unit of Hôpital Lyon-Sud and the central cytotoxic reconstitution unit. The department is composed of a 10 bed hospitalization ward; a 10 bed chemodaycare unit and a out-patient consultation unit.

Biomathematical and pharmacological Unit

The Fundamental and Translational Research is performed within the team 2 of the EMR 3738. The team is managed by Professor Michel Tod, with a more fundamental focus on in silico pharmacokinetic-pharmacodynamic (PK-PD) modelling, they also work alongside the pharmaceutical industry during cancer drug development. The team is on the cutting edge for:

  • Clinical data processing
  • Expertise in population pharmacokinetics and pharmacodynamics (PK-PD) modelling phenomenologic and mechanistic
  • Expertise in modelling complex systems
  • Expertise in biomarkers

Training

Technical Capacity of the modelling team

For data analysis and modelling a computer network capable of performing the complicated calculations with the capacity to store large amounts of information was required, without forgetting security and confidentiality. To this end we constructed a platform offering a high level of performance and security.

The laboratory is fully equipped with a network of high powered computers coupled to two internet servers provided by Dell™ allowing storage, intensive computing, confidentiality and data protection.

The established calculation tools are statistical (R®, Splus®, SAS®), mathematical (Matlab®) and specific to modelling individual pharmacokinetics and population PK-PD, NONMEM® / Monolix®(population kinetics, a mixed effect method allowing covariable analysis and the establishment of PK-PD relationships), ADAPT (individual linear kinetics, optimal sampling times), WinPOPT, PFIM, and Trial Simulator® (therapeutic trial design), WinBUGS,PKSim (PBPK model)….

Analytical expertise :

The analytical side is governed by the biochemistry laboratory, where Professor Jérôme Guitton is responsible for dose development thanks to equipment acquired by the HCL especially for the Phase I trials and use of liquid chromatography tandem mass spectrometry (LC-MS/MS).

Technical Capacity

The laboratory has the necessary equipment at its disposal to assay most of the antineoplastic agents. Essentially these are liquid or gas chromatography instruments, including:

  • 7 HPLC systems (2 dedicated for assaying antineoplastic agents) fitted with diode module UV detectors and/or fluorimetric detectors,
  • 3 systems of gas chromatography of which 2 are equipped with FIDs, and 1 equipped with mass spectrometry,
  • 2 liquid chromatography tandem mass spectrometry (LC-MS/MS),
  • 1 ICP-MS and 1 LC-ICP-MS.

The LC-MS/MS is a major analytical tool when studying metabolism due to its ability to provide both qualitative (metabolite identification) and quantitative (pharmacokinetic) information with high specificity and incomparable sensitivity, enabling the detection of tiny concentrations of analyte.