Presentation on theme: "RTL Peri-Op An Analysis of Relative Relomere Length (RTL) during Peri-operative Chemotherapy in Patients with operable Gastric or Gastro-oesophageal Junction."— Presentation transcript:
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, 23 rd October 2014)
Study Organisation Sponsored (Research Governance) - Greater Glasgow and Clyde Health Board (GGCHB Coordinated by CR-UK Clinical Trials Unit in Glasgow CR-UK CTU Glasgow are responsible for setting up, day-to-day running, analysis and presentation of results 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 gastro- oesophageal 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 gastro- oesophageal 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 gastro- oesophageal 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) Registration Form Pre-Treatment Form Treatment Form Follow up Form
CRF Completion Black ball-point pen Correction fluid etc. must not be used Errors crossed out with a single stroke, correction inserted and change initialled and dated An explanation can be written next to amendment if necessary Date format: DD / MON / YYYY Information on CRFs must be verifiable in source documents Take photocopy of all completed CRFs Original to CR-UK CTU Glasgow 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: –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 DouglasLiz-Anne Lewsley Clinical Trial Co-ordinatorProject Manager Laura.email@example.comLaura.firstname.lastname@example.org Liz-Anne.Lewsley@glasgow.ac.ukLiz-Anne.Lewsley@glasgow.ac.uk