Precision-Panc Master Protocol: Personalising treatment for pancreatic cancer.

Transcription

1 Precision-Panc Master Protocol: Personalising treatment for pancreatic cancer. Initiation Slides (Version 1 Draft 2 : 30 th October 2017) Sponsor: NHS Greater Glasgow and Clyde Chief Investigators: Dr David Chang, Prof Juan Valle Co-ordinating CTU: CRUK Clinical Trials Unit, Glasgow

2 Study Details **Please note this presentation has been prepared as part of your site initiation. These slides are a compliment to the protocol, all site staff must have read and understood the protocol and the study requirements prior to signing off the initiation acknowledgement sheet.** The Sponsor of this trial is NGS Greater Glasgow & Clyde The trial is coordinated by the CRUK CTU Glasgow and the University of Glasgow The co-chief Investigators for this trial are Dr David Chang and Prof Juan Valle. The trial is funded by Cancer Research UK and Celgene. Study will be conducted according to ICH GCP guidelines E6 Study carried out in accordance with the World Medical Association Declaration of Helsinki Ethical Principles for Medical Research involving Human Subject 1964 (as amended) Study carried out in accordance to Research Governance Framework (non- CTIMPs)

3 Study Team Chief Investigators: Project Manager: Statisticians: Pharmacovigilance: Sponsor Contact: Sponsor Pharmacist: Clinical Trial Co-ordinator: Clinical Trial Monitor: Professor Juan Valle Dr David Chang (translational lead) Judith Dixon-Hughes Jim Paul & Jamie Stobo Lindsey Connery & Pam Fergusson Joanne McGarry Paula Morrison Hannah Weir Louise Dinnett

4 Study Design The Precision-Panc Master Protocol is a portal protocol for patients with known or suspected pancreatic cancer to be accrued through multiple centres in the UK, with the option of being subsequently enrolled into PRIMUS (Pancreatic cancer Individualised Multi-arm Umbrella Study) examining different treatment regimens and/or biomarker development. Eligible patients will undergo tumour biopsy and blood collection prospectively for molecular profiling at a central laboratory and the results may be used to inform enrolment to PRIMUS studies. The trial will recruit between patients over 5 years throughout the UK

5 Study Primary Objective To establish a mechanism and framework to recruit and screen patients with pancreatic cancer to perform molecular profiling, evaluation of circulating biomarkers, and enable enrolment to Precision-Panc PRIMUS studies.

6 Study Secondary Objectives To assess the overall survival (OS) in patients enrolled in Precision-Panc and relate this to molecular profile information. To assess the safety of obtaining tumour biopsies suitable for molecular profiling within a standard patient treatment pathway. To establish a central repository of molecular profiles with accompanying phenotypic data and accompanying biospecimens for further translational research. To establish a dynamic platform for evaluation of circulating biomarkers to subsequently inform design of subsequent clinical studies.

7 Eligibility Criteria **Please refer to section 3.2 of the study protocol for full details of the eligibility criteria for the study (Brief details of the key selection criteria only is detailed on this slide)** Adult patients (age >16 years) Either: Presence of a hypodense pancreatic mass highly suspicious of primary pancreatic cancer with or without distant metastasis as assessed by a Pancreatic Multi-Disciplinary Team (MDT) Or Histologically or cytologically confirmed pancreatic ductal adenocarcinoma and its variants Patient is willing and able to undergo tumour biopsy aimed at obtaining sufficient tissue for molecular profiling. Patient is deemed suitable to receive chemotherapy and/or radiotherapy, and/or surgery pending on stage of disease at presentation Signed informed consent for Screening research tumour biopsy (Consent 1) Signed informed consent for Precision Panc Master Protocol molecular profiling (Consent 2). Please note there will be no exception to the eligibility requirements at the time of registration/randomisation. Queries in relation to the eligibility criteria should be addressed via contact with the CTU prior to registration/randomisation. Patients are eligible for the trial if all the inclusion criteria are met and none of the exclusion criteria apply.

8 Biopsy Requirements Patients will then undergo a core biopsy procedure of the primary tumour and/or metastatic lesion(s). This can be done either through a EUS procedure or percutaneously by interventional radiology depending on local expertise and clinical staging of disease. An additional blood sample must be provided at the time of biopsy. Please see the lab manual for full details of translational sampling

9 Screening / Registration Process To screen or register a patient on the trial contact the CRUK Clinical Trials Unit, Glasgow. Screening and Registration to the trial can be performed by either telephone or fax on the following numbers: Telephone Number: Fax Number: The patient s eligibility criteria will be reviewed and confirmation given that the consent for research biopsy (Consent 1) has been obtained before an initial screening ID will be allocated. Once cancer is confirmed and the patient gives consent for Master Protocol molecular profiling (Consent 2) the Glasgow CRUK CTU will be contacted a second time and a Precision-Panc Master Protocol ID will be generated All patients must be screened and registered onto the Master Protocol prior to commencement of any study procedure. With the patient s consent the participant s GP will be informed of their involvement in the trial.

10 Informed Consent Process Informed consent process: One or two original Consent Forms must be completed by a clinician (or deputy listed on delegation log) One or two originals signed and completed by the patient Date must be prior to registration Make one or two photocopies - Original to be filed in Investigator File - Original or photocopy to be given to patient (+PIS) - Photocopy to be filed in hospital notes Consent Form must not be sent to your coordinating trials office CONSENT WITHDRAWAL This is when the patient specifically asks to withdraw their consent at any point in the study. 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 on the MACRO system No further follow-up should be collected on the patient from that point onwards.

11 Process for notification of protocol deviations by sites All participating sites must notify the Sponsor (via CRUK CTU) of all deviations from the protocol or GCP immediately. The Sponsor requires a report on the incident(s) and a protocol deviation form will be provided during site initiation which should be used for informing of protocol deviations. If site staff are unsure whether a certain occurrence constitutes a deviation from the protocol or GCP, the CRUK CTU trial team and Sponsor can be contacted immediately to discuss. The Sponsor will assess all incidents with respect to the criteria of a serious breach.

12 Monitoring plan and visits Monitoring Visits/Schedule: Sites will be monitored for the Precision Panc Master Protocol at the same time as they are monitored for the PRIMUS studies that the site is recruiting too Telephone & Remote Monitoring: The time & date will be agreed with a member of the Site Study Team A pro forma covering the questions which will be covered during the telephone monitoring visit will be sent with confirmation of the agreed date. On Site Monitoring: All patient source documentation should be made available to enable Source Document Verification by the Clinical Trial Monitor. A full working day is required for on-site visits & arrangements should be in place to facilitate the monitor access on the agreed date. If sites are able to provide printed results/reports these must be filed in the source documents. If a site is using electronic data reporting systems or electronic records & hard copies are not available the clinical trial monitor must be permitted access to the system either by being issued with a temporary login or a member of staff available for the duration of the visit to facilitate electronic access to authorised reports/results. All findings will be discussed at an end of visit meeting and any unresolved issues raised as Action Points. Action Points will be followed up by the monitor until resolved.

13 Data Management The trial uses the electronic data capture system MACRO and paper screening and registration forms and paper patient history questionnaire. MACRO log ins will be required for members of staff entering data and the PI and can be requested from the CTC/PM Data Escalation Process: CRUK CTU will regularly chase outstanding data from participating sites. Routine requests for outstanding data and outstanding data queries will be performed quarterly or more regularly if required for a specific study. Sites will be routinely requested to return outstanding data and data queries within 6 weeks of receiving the queries or the CRF being due for completion.

14 Site Set- up Process CTU Glasgow - REC approval - Site Initiation Slides - Investigator File - Study consumables are required SITE - SSI - Delegation Log - Local Approval - CVs for Study Team - Clinical Trial Agreement - GCP Certificates for Study Team - Screening and registration PIS, Consent, GP Letter on trust headed paper Initiation Process Activation of site Notification by SITE ACTIVATED

15 Confidentiality All information collected during the course of the study will be kept strictly confidential. Information will be held securely on paper and/or electronically at the CRUK CTU or University of Glasgow. The CRUK CTU and University of Glasgow will comply with all aspects of the 1998 Data Protection Act and National Health Service Guidelines for storage, transmittal and disclosure of patient information. Data on patients treated on the study will be held in study case report forms (CRFs), these files will be identified by a trial number and patient initials only. Patient identifiable data (such as full name/or initials with date of birth) should not be sent on correspondence. If you need to refer to a patient use trial and patient number. Where central monitoring of source documents by CRUK CTU (or copies of source documents) are required (e.g. scan results of blood results) the personal data of the patients must anonymised on the report e.g. black out the patient s name and any other identifiable information. Where anonymisation of documentation is required, sites are responsible for ensuring no patient identifiable data is present before sending to CRUK CTU.

16 Record Retention and Archiving Arrangements for study Archiving of the trial essential documents should be performed by both the participating trial site and Sponsor. Participating sites are responsible for archiving their trial related documentation and should follow the requirements of their R&D Office in conjunction with advice from the CRUK CTU and Sponsor regarding the duration of document retention. Sites should not archive their trial documentation until they have been instructed by the CRUK CTU or Sponsor that they are able to do so. Where possible, at the time of archiving, sites will be notified of the archiving retention period. If this is not confirmed at the time of archiving, sites should not destroy archived documentation until authorisation is given from the Sponsor. The Sponsor and CRUK CTU will be responsible for archiving the Trial Master File (TMF) and all other essential trial documentation that is not held at participating trial sites as per their applicable SOPs.

17 Safety Reporting Requirements The Sponsor requires: Investigators document Adverse Events (AEs) in patient notes and the CRF as required Investigators report Serious Adverse Events (SAEs) immediately to the CRUK Clinical Trials Unit Glasgow The CTU (on behalf of the Sponsor) will make expedited reports of SAEs that meet the criteria for SRAE to the REC and Sponsor SAE References For each SAE report received for a patient a SAE reference will be allocated by CRUK CTU Pharmacovigilance team (for e.g. -1 for first event and -2 for patients second event ) and provided in an acknowledgement of each new SAE report. Where details of SAE are recorded on the CRF for e.g. Adverse Event table the SAE reference number allocated to the event should be recorded on the ecrf. CRUK CTU Pharmacovigilance Team If sites have any queries they should contact the CRUK CTU Pharmacovigilance Team who will be happy to provide advice. mvls-ctu-pv@glasgow.ac.uk Telephone number: /3968/3567

18 Safety Reporting Requirements Adverse Events Adverse Events (AEs) Investigators must record all AEs in the patient notes. AEs should be recorded on the ecrf for the following events if they are a result of a tumour biopsy (percutaneous or endoscopic) or other protocol related procedure: Post procedure pain not controlled with simple analgesia Pancreatitis Post procedure haemorrhage Wound infection Perforation Pneumothorax Anaphylactic reaction to local anaesthetic or sedation agents Death following complications from biopsy procedure

19 Safety Reporting Requirements- Serious Adverse Events Serious Adverse Events (SAEs) SAEs are only required to be reported if they are the result of a tumour biopsy (percutaneous or endoscopic) or other protocol related procedure and meet the protocol definition of serious. Serious Adverse Events (SAEs) must be reported immediately (within 24 hours of knowledge of the event) using the current version of the Master Protocol SAE report form. Sites must complete and fax the report to CRUK CTU Glasgow Pharmacovigilance (PV) on fax number SAE report forms may also be ed to mvls-ctu-pv@glasgow.ac.uk The CRUK CTU PV will create a SAE reference number and will send an acknowledgement /fax to confirm receipt of the initial report with the SAE reference number. Please contact PV if you do not receive an acknowledgement. The CRUK CTU PV will request additional information if the event is unexpected and will raise queries for any inconsistent or missing information. Completed queries must be returned within 7 working days. SAEs are required to be reported from consent for up to 30 days after the final protocol related procedure. Any event that meets the criteria of a SAE that occurs after 30 days post procedure is also required to be reported if the Investigator thinks that the SAE is related to a trial procedure. The Investigator must report such SAEs to the CRUK CTU Pharmacovigilance Office again without undue delay.

20 Safety Reporting Requirements Expedited Reporting The assessment of expectedness for SAEs and regulatory reporting will be undertaken by the CRUK CTU PV and CI. SAEs that meet the criteria or being related and unexpected will be reported to the REC within 15 days of receipt of the SAE report form. Pharmacovigilance Data Escalation Process CRUK CTU Pharmacovigilance team will regularly chase outstanding data from participating sites in relation to SAE report forms with request for data/ queries to be returned within 7 working days. If, following requests, a response is not received from site staff an escalation process will begin. Please ensure all queries for further SAE information are responded to promptly to enable the gathering of required safety data for the Sponsor to make decisions regards patient safety for this trial.

21 Other Staff The Principal Investigator has overall responsibility for the conduct of the clinical trial at the trial site. BUT All staff must comply with GCP. Staff should only perform tasks delegated to them. Staff should ensure that their details are available to the Investigator. Staff should maintain appropriate confidentiality at all times

22 Contact Details for CRUK CTU, Glasgow CRUK CTU, Glasgow Cancer Research UK Clinical Trials Unit Level 0, Beatson West of Scotland Cancer Centre 1053 Great Western Road, Glasgow, G12 0YN Project Manager (CTU) GPOL Contact Judith Dixon-Hughes David Chang Tel: Tel: