DIRECTION OF CLINICAL RESEARCH AND INNOVATION

ORGANISATION& STRUCTURE

Brochure for sponsors and

clinical research organisations

(CROs)

Version n°2: 30 April 2019General Director - Pr. Eric LARTIGAU

Director of Clinical Research and Innovation - Pr. Nicolas PENEL

INVESTIGATIONAL UNIT

CO

NTE

NTS

I. General Presentation 3

A. Areas of Clinical Research application 3

B. Activities in 2017 4

C. Quality Assurance 4

II. Practical Information 5

A. Contractual Obligation 5

B. Staff 6

1. Doctors 6

2. Research Coordinators & Technicians 6

C. Training 6

III. From feasibility to implementation of the trial 7

A. Generalities 7

B. Feasibility and selection 7

C. Clinical study group 8

D. Trial commencement 9

IV. Trial conduct 10

A. Selection and inclusion of patients 10

B. Clinical file and monitoring 10

C. Archiving 11

V. Integrated Care 11

VI. Other departments in the Oscar Lambret Center 12

A. Pharmacy 12

B. Laboratory UP2M (Anatomical pathology) 13

D. Radiotherapy 14

E. Medical Imaging 15

VII. Conclusion 16

3

The purpose of this brochure is to present the research teams dedicated to the management of clinical trials at the Oscar Lambret Center (OLC). Our research teams manage trials from set-up to close-out in accordance with current regulations and biomedical research conventions.

Research is one of the three core missions of the Oscar Lambret Center (OLC). The primary task of the Investigation Unit of the Direction of Clinical Research and Innovation (DRCI) is to coordinate the clinical studies of the OLC with, and for, the investigators of the different departments.

ENSUREthe management of biological

samples and images

The Oscar Lambret Center has been a major player in oncological clinical research for many years. The Oscar Lambret Center treats all solid tumors.

Clinical research includes any categories of study, from Phase I to Phase III with early phase studies given priority. Our center was granted National Cancer Institute CLIP² (Certified Early Phase Center) status in 2015. This certification was renewed in 2019 (for 5 years):

in partnership with Lille University Hospital, the Oscar Lambret Center is the primary site in this new wave (CLIP² for adult and child).

To facilitate multidisciplinary care for patients, we maintain relationships with the University Hospital of Lille, and other institutions in the region, for radiotherapy treatment, CLIP², patient referrals, Multidisciplinary Consultation Meetings (MCM), etc.

I. General Presentation

A. Areas of Clinical Research application

RESPOND to the sponsor’s

requests

OURACTIVITIES

PLAN AND PERFORM clinical trials

CLOSE-OUTAND ARCHIVING

clinical trials

BREAST - SARCOMAS - EARLY

PHASES OF ALL SOLID TUMOURS - HEAD AND NECK -

ALL PAEDIATRIC SOLID TUMOURS - Carcinoma of unknown primary site - Pain - Geriatrics - Palliative care - Lungs - Anaesthesia - Palliative care

- Gastrointestinal -Technological innovations in imaging, nuclear

medicine, radiotherapy.

Research Areas

2015-2018 : Number of patients with cancer code

2015 2016

6078 6235

2017 2018

6097 6444

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B. Activities in 2018

C. Quality Assurance

Interventional studies Number ofstudies

Number ofpatients enrolled

Head, neck and chest oncology: Upper Ae-ro-digestive Tract+ Lungs

20 69

General oncology: Sarcoma and rare tumors 13 160

General oncology: Urology + Digestive 21 201

Gynecological oncology 15 24

Breast cancer 19 108

Anesthesia, Recovery, Algology 1 84

Medical imaging/Nuclear medicine 1 0

Pediatrics 25 35

Radiotherapy 17 71

Psychology/Geriatrics/Palliative care 3 21

All tumors/Early phases 16 35

Total 151 808

ISO quality certification guarantees that the Clinical Research and Innovation Division’s stakeholders (patients, doctors, staff and partners) establish an excellent Quality Management System (QMS). Additionally, our QMS manages both clinical studies currently enrolling and projects sponsored by the Oscar Lambret Center.

The DRCI was inspected by the regional health authorities in 2017 and by the FDA in 2014 and no major risks were identified. The DRCI is also routinely audited by sponsors without any critical deviations reported.

2015 2017 2018CLIP2 certification

for adults and pediatrics

Renewed authorization for

adult and pediatric early phase studies

ISO 9001 certification (2015-forward) “…to

«conduct early phase clinical research in a certified

center, for sponsors (from concept to evaluation) and

investigators (from feasibility to close-out, including

patient care).”

2019

• ISO 9001:2015 follow-up audit. Certification

renewed without observations

• CLIP² certification for adult and pediatric (3rd

INCa wave)

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Please note: partnerships with pharmaceutical companies or clinical research organizations (CRO) are established to improve responsiveness and centralize administrative documents.

For a pharmaceutical sponsor, the French unique hospital contract (UHC) v2 is used. It is signed within 15 working days of receipt of the coordinators’ signed cost estimate, or within 45 days of negotiation when the OLC acts as coordinator.

At the OLC, the contract is signed in triplicate, in French (though English translations are accepted within the framework of the UCH).

Our signatories are:

• The General Director of the establishment (Professor Eric LARTIGAU);• The Sponsor;• The Principal Investigator.

No contract is signed with the OLC technical unit or any external doctors.

The preparation of documentation (confidentiality agreements, feasibility studies, agreements and cost estimates) is managed by the coordinating CRAs and Nathalie DEVIENNE, Management Assistant : n-devienne@o-lambret.fr - 00 33 20 29 59 35 / Fax: 00 33 20 29 59 71

II. Practical Information

A. Contractual Obligation

For any new study proposals to potential investigators, please contact exclusively to the following address: investigation@o-lambret.fr

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The Investigation Unit of the DRCI has a team of Study Coordinators (SCs) and clinical research technicians (TRCs). The lead and the back-up SCs are designated during the clinical study set-up.

The CR contacts liaise between the coordinating CRAs and the committee of the body they come under.

*not body committees, maintain department status **cross-disciplinary expertise

Investigators undergo TransCelerate-certified training in Good Clinical Practice (GCP). These certificates and the investigators’ CVs are available on request from:Nathalie DEVIENNE n-devienne@o-lambret.fr - Tel.: 00 33 20 29 59 35 / Fax: 00 33 20 29 59 71

Study coordinators undergo the following training :• Diploma in Clinical Research,• Good Clinical Practice certification (GCP) (TransCelerate),• IATA certification for delivering blood and tumor samples,• Use of various types of eCRF (Inform, Rave, OCRDC…).

2. Research Coordinators & Technicians

C. Training

Body committee Body committee head Clinical research contact

Head and neck Dr. M. JULIERON Dr. C. ABDEDDAIM / Dr. X. LIEM

DARA / Palliative care* Dr. A. AHMEIDI Dr. A. AHMEIDI

Digestive Dr. F. EL HAJBI Dr. F. EL HAJBI

Gynecology Dr. F. NARDUCCI Dr. F. NARDUCCI

Neurology Dr. R. MOUTTET-AUDOUARD Dr. R. MOUTTET-AUDOUARD

Pediatrics* Dr. A-S. DEFACHELLES Dr. A-S DEFACHELLES

Lungs Dr. E. DANSIN Dr. F. LE TINNIER

Sarcoma and rare tumors Dr. A. CORDOBA Prof. N. PENEL

Breast Dr. M-P CHAUVET Dr. A. MAILLIEZ

Social Science** Depending on the project

All tumors** Prof. N. PENEL

Urology Dr. D. PASQUIER Dr. A. CARNOT

Since the new 2018-2022 Medical and Scientific Project was implemented, the medical organization structure is comprised of departments and body committees to efficiently monitor patient care.Continuously striving to improve, and in conjunction with the new Medical and Scientific Project, Clinical Research (CR) contacts have been appointed in these departments and body committees.

All the doctors practicing at the OLC are involved in clinical research as national coordinators and/or investigators.

B. Staff

1. Doctors

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When sending a project proposal to the doctor, adding the generic e-mail address investigation@o-lambret.fr will accelerate our response to your request.

For pharmacological questions, contact the Clinical Trial Pharmacist, Dr. Stéphanie DELBEY, Head Pharmacist of Clinical Studies s-delbey@o-lambret.fr

Pre-selection visits are conducted in a group consisting of the Principal Investigator (PI), managing pharmacist, and one of the clinical studies coordinator.

III. From feasibility to implementation of the trial

A. General information

B. Feasibility and selection

Feasibility studies are completed by the Investigator, the respective technical platform manager concerned with scientific elements, and the investigation coordinator for logistic and administrative elements.

Contact: Investigation coordinating CRAs - investigation@o-lambret.fr

Nathalie DEVIENNE n-devienne@o-lambret.fr is your contact for:

• Regulatory documents (FDF, FDA 1572 confidentiality agreements, etc.) • Administrative documents, • Co-investigator declarations, • CV requests, • Standards & accreditation,• Planning of study set-up.

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The Clinical Studies Commission (CSC) evaluates the projects to be implemented through the OLC’s DRCI. This commission usually meets once a month.If needed, the calendar can be requested from Nathalie Devienne n-devienne@o-lambret.fr

The CSC has the following members:• The General Director of the Oscar Lambret Center• The DRCI Director• The Officer for external relations, development and quality• The Clinical Research contacts

In order for the project to be evaluated by the CSC, the following prerequisites must be met: selection accepted by the sponsor; study documents submitted to the relevant authorities (ANSM, Ethics Committee, etc.); laboratory manual, investigator’s brochure if drug trial, financial appendix, study summary file.

C. Clinical study group

Receipt of a feasibility study by the investigator/RC coordinator

Transfer of information to the DRCI

Creation of a feasibility studyCompletion of the “project monitoring” table

Sponsors response ArchiveRefusal

Refusal

Agreement

Acceptance

Archive

Send the completed feasibility questionnaire

Appointment for a pre-selection visit

Pre selection visit

Creation of the file for Clinical Studies Commission (CSC)

Passed to CSC

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New: the project can be submitted to the CSC and regulatory authorities simultaneously

The Clinical Studies Commission’s opinion can be:

• Unfavorable: no implementation, the project is archived,• Suspended: a request for additional information is made in writing by the investigator,

who is in charge of exchanging information with the sponsor; a written, point-by-point answer is expected,

• Favorable: the project is accepted.

Whatever opinion is reached, the sponsor will be informed first by e-mail.

The trial will commence when we have received:• The signed agreement• CSC and OLC approval• Nomination of the study coordinator who will lead study conduct

This visit is planned by Nathalie DEVIENNE in connection with the investigator and the study coordinator in charge of the study.

To reach the pharmacy, you may contact the Clinical Trial Pharmacist, Dr. Delbey, on 00 333 20 29 59 06 or s-delbey@o-lambret.fr.

D. Trial commencement

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IV. Trial conduct

Clinical trial protocols are conducted in a strict ethical and regulatory environment to ensure patient safety and quality of care.

A procedure for reporting of serious adverse events without delay is used, (including outside working hours).

MCM (Multidisciplinary Consultation Meetings) and departmental meetings are organized by pathology each week. These meetings identify potential patients for inclusion in clinical trials.

The investigators send the list of patients to the study coordinator (SC) so that SC can exhaustively check the inclusion and exclusion criteria from the computerized patient record.

Patients who meet the protocol criteria will be referred to the DRCI Integrated Care Unit for a consultation with an investigator, who will present the study and obtain consent.

All the studies are referenced on the center’s website, so pre-screening is possible after transmission of a file to the following email address: investigation@o-lambret.fr.

A. Selection and inclusion of patients

A monitoring visit may be organized with the reference study coordinator of the particular study (preferably by e-mail). During the monitoring visit, the clinical team can make itself available according to the previously established schedule. File storage is accessible through restricted access protocols.

The DRCI has a room dedicated to monitoring visits, equipped with computers (internet connection) with limited access to the monitored study via a specific password-protected account. Medical records are in electronic format (DxCare).

During monitoring visits, the monitor must sign a confidentiality agreement.

Our privacy rules are as follows:• Personnel access codes are issued, upon request, to

the sponsors’ representatives,• Read-only access is provided for sponsors’

representatives. • Access available to patient-specific records for

participants who have given prior consent to participate in the clinical trial,

• An audit trail is available upon request by the sponsor or the health authorities.

B. Clinical file and monitoring

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Study documents are archived at the end of the trial in accordance with regulations, sponsor’s practices, and biomedical research conventions.

The OLC retains study documents within the institution; first in a pre-archiving room, and later in a final archiving room. These archives are of limited access.The premises have pest management, hygrometry monitoring and temperature control. Temperature records are available upon request.

Each sponsor is systematically contacted before any file destruction

C. Archiving

V. Integrated Care

The Investigation Unit has an integrated care team, which provides care to the patients enrolled in trials.

Team: 4 nurses + 1 referral nurse + Sophie COSTA, Clinical trial research nurse coordinator s-costa@o-lambret.fr - Tél. : 03 20 29 58 39 / Fax : 03 20 29 55 59

Integrated care infrastructure:

• 10 beds, 4 armchairs and 4 consultation rooms,• 1 sampling room,• 1 technical room,• 3 equipment storage rooms,• 1 medicine refrigerator,*• Emergency cart equipped with a defibrillator, plus intubation and ventilation equipment,• 12-lead ECG devices,*• Vital sign monitors (pulse, blood pressure, temperature),*• Scales,*• 2 refrigerated centrifuges,*• 2 -20°C freezers and 2 -80°C freezers* connected to safety controls and equipped with

Fischer ThermoClient temperature monitoring software with e-mail alerts. (Temperature curves available upon request.).

*All of these materials are routinely maintained All rooms are secured by badge or key access.

Nurses undergo annual emergency training.

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The OLC Biomedical Department is responsible for the maintenance and calibration of integrated care equipment for all other departments (anatomical pathology, pharmacy). In accordance with our ISO 9001 certification, there is an interface contract between the DRCI and the Biomedical Department to guarantee that the latter performs its mandatory operations.

EMERGENCIES:

VI. ther departments in the Oscar Lambret CenterDepartments are composed of a medical department (Head: Pr Nicolas PENEL), a surgical department (Head: Dr Eric LEBLANC) and different other departments constituting a highly efficient technical team.

Opening hours: 8:30am-5:00pm

Clinical Trial Pharmacist:Docteur Stéphanie DELBEY : s-delbey@o-lambret.fr Tel.: 00 333 20 29 14 32 / Fax: 00 333 20 29 59 78Address: Pharmacie à Usage intérieur (PUI) – Secteur Etudes Cliniques3 rue Frédéric Combemale - 59020 Lille Cedex

The internal pharmacy is authorized to work for clinical trials.

According to the protocol and the sponsor’s requirements, the pharmacy can handle:• Provision (via the sponsor, or directly from the pharmacy),• Reception,• Storage,

• Room temperature storage• A narcotic safe (15 to 25°C)* in a temperature controlled room,• Refrigerators (2 to 8°C)*,• Freezer (-37.5 to -21°C)*,

• Storage management,• Drug preparation (if applicable),• Dispensing,• Disposal (either destroyed by our service provider or returned to the sponsor),• Digital document archiving

*This equipment is regularly checked.

A. Pharmacy

N.B.: children and young adults participating in clinical trials are managed by the Pediatric Oncology Unit (hospitalization or outpatient), which has all necessary equipment.

An on-call doctor is available 24 hours per day for patients participating in clinical trials. In the event of an emergency, a protocol has been established between the OLC and the University Hospital Center of Lille (contactable by dialing 1515).If hospitalization is required for a patient participating in a clinical trial, a site-authorized room is available.For patients included in Phase I trials, each participant is given an index card with instructions on how to deal with an adverse event.

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The pharmacy is responsible for the feasibility, implementation, delivery and organization of monitoring visits. Contact Dr. Stéphanie Delbey s-delbey@o-lambret.fr to make an appointment. Copy prepecpharma@o-lambret.fr in the email for best results.

The pharmacy provides a room for monitoring visits and the close-out visit. Two slots are available per day 1:30pm – 3: 00pm and 3:00pm – 5:00pm.

Only the administrative closing letter documents the official end of the clinical trial.

This department houses the activities of a biological resource center (BRC), anatomical pathology activities (UP2M) and hemovigilance and biological activities.

Primary activity: onco-pathology. • Active volume of the UP2M: around 7,500 test requests per year• Active volume of liquid BRC: around 1,100 tubes per year

2 principal functions of the UP2M: • Diagnosis of tumor lesions• Tumor prognosis• Teaching anatomical pathology• Research in partnership with the DRCI, INSERM units, Lille University Hospital’s Anatomical

Pathology Center (Regional Oncology Reference Center tumor library) and the region’s 3 cancer centers

Principal function of the liquid BRC:• Pre-testing for the DRCI

Principal functions of the hemovigilance and biological unit:• Bone marrow cytology• Blood gases and hemobiology• Consultants on biological matters to assist the Center’s clinicians

B. Laboratory UP2M (Anatomical pathology)

DEPARTMENT HEAD: Docteur Guillaume MARLIOTCLINICAL RESEARCH CONTACT: Docteur Stéphanie DELBEY

Via Nathalie DEVIENNE : n-devienne@o-lambret.fr - 00 33 20 29 59 35

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Equipment• Accelerators:

* Darpac is the radiotherapeutic contact.

C. Radiotherapy

Machine Brand of treatment Mechanism of treatment

Clinac1 Accuray Cyberknife M6

Clinac2 Varian Clinac 23EX

Cyberknife Accuray Cyberknife M6

Tomo 1 Tomotherapy HI ART

Tomo 2 Tomotherapy HI ART

Tomo 3 Tomotherapy TomoHD

Darpac* Nucletron Darpac2000

Dedicated simulation scanner (brand) Model Year of scanner manufacture

Toshiba AQUILION 16 LB 2009

All biological analyses are conducted at Lille University Hospital’s Anatomical Pathology Center.

The laboratories accreditations are available on the Center of Pathology & Biology website (http://biologiepathologie.chru-lille.fr/politiquequalite/).

The standards and the Laboratory Director’s CV are available upon request from Nathalie DEVIENNE n-devienne@o-lambret.fr

• Scanners:

DEPARTMENT HEAD: Docteur Yves-Marie ROBINCLINICAL RESEARCH CONTACT: Delphine BERTIN

Via Nathalie DEVIENNE : n-devienne@o-lambret.fr - 03 20 29 59 35

DEPARTMENT HEAD: Docteur Xavier MIRABELCLINICAL RESEARCH CONTACT: Docteur David PASQUIER

Via Nathalie DEVIENNE : n-devienne@o-lambret.fr - Tél.: 03 20 29 59 35

1515

Equipment

• MRI (Siemens Magnetom VIDA 3 tesla) ; GE MRT 750 3T• CT Scanner : SIEMENS Sensation 16 – Somaton • Power injector : Mallinckrodt (Optivantage DH)

Evaluation des tumeurs selon les normes Recist 1.1, RANO (tumeurs cérébrales) et ITMIG (tumeurs thymiques)

Tumors are evaluated according to the following standards; Recist 1.1, irRECIST, RANO (brain tumors), ITMIG (thymic tumors) and CHOI (hepato-carcinomas)

Weekly availability for clinical research: • Scanner: 3 slots/Monday, 3 slots/Wednesday, 1 slot/Friday • MRI: 1 slot/Friday

Equipment for nuclear medicine: • PETSCAN: G.E. Pet Discovery 690 (installed September 2011)• Bone scintigraphy: GE VARICAM XELERIS 3• Cardiac scintigraphy

D. Medical Imaging

DEPARTMENT HEAD: Docteur Luc CEUGNARTCLINICAL RESEARCH CONTACT: Docteur Luc CEUGNART

Via Nathalie DEVIENNE : n-devienne@o-lambret.fr - Tél.: 03 20 29 59 35

Contact usTel : 03 20 29 59 35 ou 03 29 59 18 - Fax : 03 20 29 59 71

Mail : investigation@o-lambret.frDIRECTION OF CLINICAL RESEARCH AND INNOVATION 3, rue Frédéric Combemale - BP

307 - 59020 LILLE Cedex Francewww.centreoscarlambret.fr

DRCI values

RESPONSIVENESS

ANTICIPATIONOUR

VALUES

ORGANIZATION

COMMUNICATION

VII. Conclusion

The DRCI is available to answer any questions, or provide any further information. Please contact us at investigation@o-lambret.fr