Transcript Document

RTL Peri-Op
An Analysis of Relative Relomere Length (RTL)
during Peri-operative Chemotherapy in Patients
with operable Gastric or Gastro-oesophageal
Junction Adenocarcinoma
(Version 3, 23rd October 2014)
Study Organisation
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Sponsored (Research Governance) - Greater Glasgow
and Clyde Health Board (GGCHB
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Coordinated by CR-UK Clinical Trials Unit in Glasgow
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CR-UK CTU Glasgow are responsible for setting up,
day-to-day running, analysis and presentation of
results
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Chief Investigator is Professor Jeff Evans, The
Beatson West of Scotland Cancer Centre (BWoSCC)
Study Team
• CRUK CTU Team
– Chief Investigator: Professor Jeff Evans
– Trial Statistician: Jim Paul
– Project Management: Liz-Anne Lewsley
– Clinical Trial Co-ordinator: Laura Douglas
– Laboratory Contact: Jennifer Walker
Study Summary
• Multi-centre, open, non-randomised study.
• Study recruitment: 153 patients
• Study population: patients with operable gastric or gastrooesophageal junction adenocarcinoma who are about to undergo
peri-operative chemotherapy with either the ECF/EOF or
ECX/EOX regimens (patients randomised to the NCRN STO3
study to receive ECX + bevacizumab will also be eligible).
• Timelines:
- Opened to recruitment May 2010
- Planned accrual completion is December 2017
Objectives & Endpoints
Primary Objective
• to analyse Relative Telomere Length (RTL) in blood samples taken from patients during
peri-operative chemotherapy for operable gastric or gastro-oesophageal junction
adenocarcinoma. This will allow us to dtermine if the baseline (pre-treatment) RTL
correlates with patient outcome as measured by relapse-free (RFS) and overall survival
(OS)
Secondary Objectives
• to determine if the baseline (pre-treatment) RTL correlates with “tumour response” as
measured by down-staging of the primary tumour with the pre-operative component of
chemotherapy with pathological staging at subsequent resection or with repeat radiological
staging in the event of progressive disease so that the tumour is inoperable)
• to analyse changes in markers associated with cellular senescence in blood samples taken
from patients during peri-operative chemotherapy for operable gastric or gastrooesophageal junction adenocarcinoma.
These will include cathelicidin-related
antimicrobial protein (CRAMP), EF-1a, stathmin, and chitinase 3-like protein 3
Tertiary (Exploratory) Objectives
• to analyse changes in CK-18 in blood samples taken from patients during peri-operative
chemotherapy for operable gastric or gastro-oesophageal junction adenocarcinoma as a
marker of drug-induced cell death by apoptosis.
• to analyse changes in senescence-associated micro-RNAs in blood samples taken from
patients during peri-operative chemotherapy for operable gastric or gastro-oesophageal
junction adenocarcinoma.
Patient Registration
Procedure for all sites
• Check that patient has given written informed
consent
• Check that patient fulfils eligibility criteria
• Complete Registration Form
• PHONE or FAX registration details to the CR-UK
CTU Registration/Randomisation Service
• Each patient registered will be allocated a
unique trial number (3-digits)
Registration/Randomisation
Service
CRUK CTU Glasgow registration/randomisation service:
Tel: 0141 301 7215
Fax: 0141 301 7219*
08:30 –17:00 Mon–Thurs,
08.30-16.30 Friday (except public holidays)
*Faxes received outside of office hours will be processed the
next working day
Site Set-up
• CR-UK CTU Glasgow
- Main REC approval (Glasgow)
- Overall Management Approval
(Glasgow)
- Site Initiation Calls/Meetings
- Investigator File
• SITE
- Staff Contact & Responsibilities
Sheets
- SSI / R&D (Management)
- Investigator CVs
- Participating Site Agreement
- GCP Certificates for PIs
- PIS, Consent, GP Letter etc on local
headed paper
Initiation Call
Notification by email
SITE ACTIVATED
Inclusion Criteria
• Histologically or cytologically confirmed gastric or gastrooesophageal junction (including Type 1 lower oesophageal)
adenocarcinoma
• Patients who are considered to have operable disease as
determined by the MDT (Multi-Disciplinary Team) and who are
candidates for peri-operative chemotherapy with either the
ECF/EOF or ECX/EOX (epirubicin, cisplatin/oxaliplatin and
capecitabine) regimens. Additionally, patients randomised in the
NCRN STO3 study to receive ECX + bevacizumab will also be
eligible
• Written informed consent
• Age >18 years
• Able to comply with study protocol.
Exclusion Criteria
• Any evidence of any medical or psychiatric disorders that would be a
contra-indication to venesection
• Women who are pregnant or lactating
• Patients who have had systemic anti-cancer therapy or radiotherapy
within the previous 6 weeks
• Life expectancy < 3 months
Informed Consent Process-1
• Two original Consent Forms must be completed by a clinician (or
deputy listed on Staff Contacts & Responsibilities Sheet)
• Two originals signed and completed by the patient
• Date must be on or prior to registration
• Make one photocopy
- Original to be filed in Investigator File
- Original to be given to patient (+PIS)
- Photocopy to be filed in hospital notes
• Consent Form must not be sent to the CR-UK coordinating trials
office
Informed Consent Process-2
• Errors noticed after consent
- Add explanatory note/file note
• New version of Patient Information Sheet must be provided to
patients consented with previous version*
- Give to all patients regardless of treatment stage either by post or
during clinic visit
• Patients who are still on study will be required to repeat the consent
process using the updated form*
• If not appropriate to re-consent patient (i.e. patient terminally ill)
make a note on the re-consenting log
* Due to the nature of this study, reconsent is unlikely to be an issue.
Case Report Forms (CRFs)
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Registration Form
Pre-Treatment Form
Treatment Form
Follow up Form
CRF Completion
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Black ball-point pen
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Correction fluid etc. must not be used
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Errors crossed out with a single stroke, correction inserted and change
initialled and dated
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An explanation can be written next to amendment if necessary
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Date format: DD / MON / YYYY
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Information on CRFs must be verifiable in source documents
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Take photocopy of all completed CRFs
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Original to CR-UK CTU Glasgow
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CRF completion guidelines will be supplied
Consent Withdrawal
• This is when the patient specifically asks to withdraw their consent
at any point in the study
• Ensure that the level of consent withdrawal is clearly documented in
the source data
• If this occurs:
– Document clearly in the patient notes that the patient has
withdrawn consent, the level of consent withdrawal and the
reason (if the patient has given any);
– Complete the consent withdrawal notification form ;
– Send the consent withdrawal notification form to the CR-UK CTU
– No further follow-up should be collected on the patient from that
point onwards.
Sample Collection (1)
•20mls of venous blood will be taken at the
following time-points:
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Baseline (post registration)
Day 1 of each cycle of pre-op chemotherapy
On completion of pre-op chemotherapy
Prior to post-op chemotherapy
Day 1 of each cycle of post-op chemotherapy
Where possible, at each follow up visit
Disease relapse
Sample Collection (2)
•Tubes, labels and worksheets will be provided
•Blood samples will be labelled with the patient’s trial no, initials along
with timepoint, date and time the sample was taken
•Buffy coats will be prepared at each collaborating centre and buffy coats
and plasma will be stored at -70°C
•Collection will be transferred to the Analytical Services Unit, Wolfson
Wohl Cancer Research Centre, University of Glasgow, at regular
intervals (depending on storage capacity at sites)
• See Lab Manual for further details
Quality Assurance
Quality Assurance will be maintained by the following requirements and
activities:
•Trial Investigators and Site Staff must ensure that the trial is conducted in
compliance with the protocol, Good Clinical Practice (GCP) and the applicable
regulatory requirements
•No on site monitoring will be performed however central monitoring of trial data
will be performed by the Trial Statistician and the Clinical Trial Co-ordinator
•The CTU will control data consistency and data quality by entering trial data
onto the CTU trial database. Computerised and manual consistency checks will
be performed and queries issued in cases of inconsistency or missing
information. A full audit trail of any changes to the database will be maintained
•The Trial Management Group will ensure the trial is being managed according
to protocol, GCP and regulatory requirements (the Trial Management Group will
oversee the running of the study and meet if and when necessary)
Ethical and Regulatory Standards
• This study conducted according to ICH GCP guidelines and CR-UK
CTU (Glasgow) SOPs
• This study is carried out in accordance with the World Medical
Association Declaration of Helsinki (1964) and the Tokyo (1975),
Venice (1983), Hong Kong (1989), South Africa (1996) amendments
Contact Details
CR-UK CTU, Glasgow
Cancer Research UK Clinical Trials Unit
Level 0
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow, G12 0YN
Tel: +44(0) 141 301 7231
Fax: +44(0) 141 301 7228
Laura Douglas
Clinical Trial Co-ordinator
Liz-Anne Lewsley
Project Manager
[email protected]
[email protected]