Transcript Document

SCOT
Short Course Oncology Therapy
A Study of Adjuvant Chemotherapy in
Colorectal Cancer
Study Organisation
• Sponsored by Greater Glasgow and Clyde Health Board (GGCHB)/
University of Glasgow (GU)
• Coordinated by CR-UK Clinical Trials Unit in Glasgow and Oncology
Clinical Trials Office (OCTO) in Oxford
• CR-UK CTU Glasgow and OCTO are responsible for setting up,
day-to-day running, analysis and presentation of results
• Chief Investigator is Professor Jim Cassidy
• Supported by a grant from the MRC
Study Team
• CR-UK CTU Glasgow Team
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Chief Investigator: Professor Jim Cassidy
Protocol Development and Co-Investigator: Dr Claire Kelly
Trial Statistician: Mr Jim Paul
Project Management: Mrs Andrea Harkin
Pharmacovigilance: Mrs Lindsey Connery/Miss Katie Nocher
Quality Assurance: Mrs Lindsey Connery
Clinical Trial Co-ordinators: Ms Karen Wilson/ Mrs Sian Shirley
Clinical Trial Monitor: Laura Alexander
• Oncology Clinical Trial Office (OCTO), Oxford Team
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Co-investigator: Dr Rachel Midgley
Project Management: Mrs Sarah Pearson
Quality Assurance: Dr Joanna Black
Clinical Trial Co-ordinator: Ms Michelle Masterson
Clinical Trial Administrator: Ms Gaynor Bates
Clinical Trial Support Officer: Mr Matthew Goff
Clinical Trial Monitors: Christine Harvey & Zia Sherrell
Study Summary
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Study design: phase III, randomised controlled, two arm, multi-centre,
non-inferiority
Study treatment:
Randomise
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STANDARD
24 weeks
XELOX/ OxMdG
EXPERIMENTAL
12 weeks
XELOX/ OxMdG
Chemotherapy
[4750 patients]
Chemotherapy
[4750 patients]
Study recruitment: 9500 patients over 5 years (150 sites in the UK)
Study population: patients with colorectal cancer
Timelines:
- Recruitment started in March 2008
- Planned accrual completion is March 2013
- Trial analysis and publication planned for 2016
- Trial duration of 7 years
Objectives & Endpoints
Objectives
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Assessment of the efficacy of 12 weeks of treatment vs 24 weeks of
treatment and comparison of the associated toxicity
Economic analysis to assess the cost-effectiveness of the two treatment
alternatives
Comparison of two randomisation methodologies
Endpoints
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Primary Endpoint:
- Disease free survival (3 year)
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Secondary Endpoint:
- Overall survival
- Cost-effectiveness
- Toxicity
- Quality of life
Site Registration Process
All sites will be randomised to Upfront Randomisation after a
decision made by the Trial Steering Committee (June 2009)
- Upfront: Randomisation at commencement of adjuvant treatment
to either 24 or 12 weeks of chemotherapy
• Prior to June 2009 some sites were randomised to the delayed
randomisation time point.
- Delayed: Randomisation after 12 weeks of adjuvant treatment to
either stopping, or continuing with a further 12 weeks of
chemotherapy
Site Registration Process
• From the outset of the trial it was specified that a decision would be
made in relation to the 2 randomisation time points approx 1 year
after the study opened to recruitment.
• The independent members of the TSC decided that the study should
continue with upfront randomisation time point only for the remaining
duration of the trial.
Reason for Amendment to Randomisation
• The decision was based on the data presented in the first interim
analysis report.
• The data showed a 32% drop out rate of patients prior to the
delayed week 12 randomisation, compared to a 7% dropout of
patients stopping treatment before completing 12 weeks of
treatment on the upfront randomisation arm.
Upfront
Fully resected high-risk stage II/Stage III colorectal cancer
Prior to treatment
Register/ Randomise
Standard Arm
24 weeks
adjuvant chemotherapy
Study Arm
12 weeks
adjuvant chemotherapy
Follow-up (max 7 years)
Site Registration Process
• Prior to site activation, a site questionnaire will need to be
completed. The questionnaire will require the following information:
- List of all the sites that the PI is responsible for and which are
going to participate in SCOT.
- Responsible CTU for your site.
- Which sites are willing to participate in the QoL questionnaires.
- Estimate the total annual recruitment for all the listed hospitals.
• Return the questionnaire to CTU Glasgow by Fax.
• Fax Number +44 (0) 141 301 7192
Stratification Factors
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Centre
Choice of regimen
Gender
Disease site
T-stage
N-stage
Treatment arms
• Arm A (Standard treatment) - 24 weeks of XELOX/OxMdG
chemotherapy
• Arm B (Experimental treatment) - 12 weeks of XELOX/OxMdG
chemotherapy
• Dose and administration of XELOX – 3 weekly cycle
- Oxaliplatin 130mg/m2 IV on day 1
- Capecitabine 1000mg/m2 PO twice daily for 14 days
• Dose and administration of OxMdG – 2 weekly cycle
- Oxaliplatin 85mg/m2 IV on day 1 concurrently with
- I-folinic acid 175mg or folinic acid 350 mg followed by
- 5-FU 400mg/m2 IV bolus injection over 5 minutes followed by
- 5-FU 2400mg/m2 IV continuous infusion over 46 hours
Dose Guidelines for XELOX
Regimen
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At randomisation you will be asked for the patient’s starting dose of
Capecitabine.
Patients with a creatinine clearance of 30-50mls/min must commence
treatment with capecitabine at 75% of the full dose.
Patients > 70 years of age should be considered for treatment with
capecitabine at 75% of the full dose but, in light of differences in standard
practice between sites, this will be left to the discretion of the Investigator
depending on the fitness of the individual patient. The decision not to dosereduce must be documented in the patient notes.
At the Investigator’s discretion, patients can be commenced on a minimum
starting dose of capecitabine of 800 mg/m2 if clinically indicated. The
starting dose of capecitabine will be requested at baseline
registration/randomisation.
Capecitabine dose banding tables are provided in appendix 3 of the
protocol.
Site Set-up
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CTU Glasgow/ OCTO
- Main REC approval (Glasgow)
- MHRA approval (Glasgow)
- Site Initiation Calls
- Investigator File
- Pharmacy File
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SITE
- Staff Contact & Responsibilities Sheets
- SSI
- R&D Approval
- Investigator CVs and Lead Pharmacist
- Clinical Trial Agreement
- GCP Certificates for PIs
- PIS, Consent, GP Letter etc on Trust
headed paper
- Site Randomisation questionnaire
Initiation Call
Site Randomised
Notification by email
SITE ACTIVATED
Study Drug
• All IMPs for use in this trial should be taken from existing pharmacy
shelf stock. There is no provision for funding, reimbursement or
discounted stock
• IMPs should be stored under the correct conditions as per the SmPC
• All products used in this study are licensed medications and will not
be labelled specifically for the study
• IMP accountability logs will be provided for use, these must be
maintained for the duration of the study and must be kept in the study
pharmacy file
• Patients should be asked to return any unused capecitabine tablets
at each study visit
Pharmacy File
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Contact Information
Study Summary
Randomisation
Protocol
Ethics and Regulatory documents
Critical Documents
Subject Information Documents
Monitoring
Drug Information
GCP guidelines
Study correspondence
Monitoring Plan
• All patients monitored for:
– Consent
– Stratification variables
– Treatment detail
• Recurrences/deaths/SAEs will be monitored as per
SCOT monitoring plan.
• Pharmacy visit.
• Monitoring of Site File.
Ethical and Regulatory Standards
• SCOT is conducted according to ICH GCP guidelines and CTU/
OCTO SOPs
• SCOT is conducted in accordance with the EU Directive 2001/20/EC
• Trial 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
OCTO, Oxford
Oncology Clinical Trials Office
Depart of Clinical Pharmacology
Old Road Campus Research Building
University of Oxford
Old Road Campus
Off Roosevelt Drive
Headington
Oxford, OX3 7DQ
Tel: +44(0) 186 561 7018
Fax: +44(0) 186 561 7010
E-mail: [email protected]
CR-UK CTU, Glasgow
Cancer Research UK Clinical Trials Office
Level 0
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow, G12 0YN
Tel: +44(0) 141 301 7191
Fax: +44(0) 141 301 7184
E-mail: [email protected]