Presentation on theme: "PHARMACY INITIATION SLIDES"— Presentation transcript:
1PHARMACY INITIATION SLIDES NiCCC (G143)(ENGOT-GYN1)A Randomised Phase II study Of Nintedanib (BIBF1120) Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or EndometriumEudraCT Number:Protocol Number: NiCCC2013ISRCTNPHARMACY INITIATION SLIDES(Version th Feb 2015)
2******************************************************************* Trial DetailsThe trial is an NCRN/Boehringer Ingelheim (BI), collaborationThe trial is being co-ordinated via the Cancer Research UK Clinical Trials Unit, GlasgowSponsor of the trial is Greater Glasgow Health Board (GGHB)The trial will also open across Europe via collaborations with the EORTC, the NSGO and ARCAGY-GINECOThe Chief Investigator is Dr Ros Glasspool of the Beatson West of Scotland Cancer Centre. The International Chief Investigator is Dr Mansoor Mizra of Copenhagen University HospitalThe trial is being funded by an educational grant from Boehringer Ingelheim (who are also providing drug supply of Nintedanib) and is endorsed by CTAAC (Cancer Research UK)*******************************************************************Please note this presentation has been prepared as part of your site initiation training. These slides are a compliment to the protocol, all site staff must have read and understood the protocol and the trial requirements prior to signing off the initiation acknowledgment sheet
3Trial Team Chief Investigator : Dr Ros Glasspool International Chief Investigator: Dr Mansoor MizraCo-Investigator/Translational Research Co-ordinator: Professor Ian McNeishTrial Statistician: Jim PaulProject Manager: Claire LawlessPharmacovigilance: Lindsey Connery / Susannah RedfordClinical Trial Coordinator: Laura DouglasClinical Trial Monitor: Calum InnesSponsor Pharmacist Dr Samantha Carmichael / Paula Morrison
4Pharmacy Initiation Protocol and treatment overview IMP presentation and managementNiCCC IMP Stock Control ApplicationSite initiation processPost site activation and monitoring arrangements
6Population and Aims Trial population 120 patients with progressive or recurrent ovarian clear cell carcinoma, or progressive or recurrent endometrial clear cell carcinoma. The primary diagnosis must be histologically confirmed and central pathological review of the presenting tumour or biopsy of relapsed disease must find at least 50% clear cell carcinoma with no serous differentiationTrial AimsPrimary Objective:The primary endpoint for efficacy is progression free survival as defined by RECIST 1.1 criteria. Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death, which ever occurs earlierSecondary Objectives:Includes:Overall survival (OS)Disease Control RateToxicityQuality of Life.Q-TWiST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment)
7Trial Eligibility (1) Key Inclusion Criteria: Progressive or recurrent ovarian clear cell carcinoma, or progressive or recurrent endometrial clear cell carcinoma. The primary diagnosis must be histologically confirmed and central pathological review of the presenting tumour or biopsy of relapsed disease must find at least 50% clear cell carcinoma with no serous differentiation. Progressive disease as defined by RECIST 1.1Failure after ≥1 prior platinum containing regimen which may have been given in the adjuvant setting. For patients with ovarian clear cell carcinoma, progression must have occurred within 6 calendar months of their last platinum doseECOG Performance status of ≤2Life expectancy of >3 monthsAdequate hepatic, bone marrow coagulation and renal functionFemale and > 18 years of ageSee study protocol for full inclusion/exclusion criteria
8Trial Eligibility (2) Key Exclusion Criteria: Prior treatment with Nintedanib or other angiogenesis inhibitor/VEGF targeted therapy, except for prior treatment with bevacizumab which is permittedTreatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not affect target lesions, and the reason for the radiotherapy does not reflect progressive diseasePrevious treatment with the chemotherapy regimen selected as the control arm by the investigator. (Prior therapy with paclitaxel given on a three weekly regimen is permitted for patients receiving weekly paclitaxel. Prior therapy with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel. Prior weekly paclitaxel for relapsed disease is not permitted).Other malignancy diagnosed within 5 years of enrolment with exceptionsPatients with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgement of the investigator, would make the patient inappropriate for entry into this trial.Symptoms or signs of gastrointestinal obstruction or any other gastro-intestinal disorders or abnormalities, including difficulty swallowing, that would interfere with drug absorption.Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including known hepatitis B and/or C infection and HIV-infection
9Trial Eligibility (3)Key Exclusion Criteria continued:Symptomatic CNS metastasis or leptomeningeal carcinomatosisKnown, uncontrolled hypersensitivity to the investigational drugs or their excipientsSignificant cardiovascular diseaseHistory of major thromboembolic event unless on stable therapeutic anticoagulationHistory of CVA, TIA or subarachnoid haemorrhage or clinically significant haemorrhage in past 6 monthsMajor injuries or surgery within the past 28 days prior to start of trial treatment with incomplete wound healing and/or planned surgery during the on-treatment trial periodPregnancy or breastfeeding. Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatmentPatients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwardsRadiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vesselsAny psychological, familial, sociological or geographical consideration potentially hampering compliance with the trial protocol and follow up schedule; those considerations should be discussed with the patient before registration in the trialSee study protocol for full inclusion/exclusion criteria
10Central Pathology Review Criteria and Eligibility Criteria met Trial DesignA multi-centre, randomised, open label phase II trial90 patients with progressive or recurrent clear cell ovarian and up to 30 patients with clear cell endometrial cancerRegistrationCentral Pathology Review Criteria and Eligibility Criteria metRandomisationControl ArmPhysicians choice of standard chemotherapy, from list below*.Experimental ArmNintedanib 200mg BD continuously until progression or withdrawal from trialAssessmentsClinical:At screening, Day 1 and then every 4 weeks until week 24 and then every 8 weeks.CA125:At screening, day 1 and every 4weeks until week 24 then every 8 weeks until progressionCT ScansScreening, and every 8 weeks until week 48 or until progressionAssessmentsClinical:At screening, Day 1 of each course of chemotherapyCA125:At screening and day 1 of each cycle during treatment then every 8 weeks until progressionCT ScansScreening, and every 8 weeks until week 48 or until progressionPrimary Endpoint: PFSSecondary Endpoints: OS, QoL, QTWIST, ORR, & DCR at 12 weeks
11Treatment and Duration Experimental ArmNintedanib (BIBF1120) 200mg twice daily PO, continuously, until progression or withdrawal from the treatment.Control ArmThe chemotherapy regimen will be physician’s choice from the list below. The planned regimen (if allocated to the control arm) must be declared prior to randomisation:Ovarian Cancer Patients:Paclitaxel (80mg/m2) IV Day 1, 8, 15 every 28 days, x6 cyclesPegylated Liposomal Doxorubicin (PLD) (40mg/m2) IV every 28 days, x6 cyclesTopotecan (4mg/m2) IV Day 1, 8, 15 every 28 days, x6 cyclesEndometrial Cancer Patients:Carboplatin (AUC 5) and Paclitaxel (175mg/m2) IV every 21 days, x6 cyclesDoxorubicin IV (60mg/m2) every 21 days x6 cycles
12Nintedanib Dose Delays Treatment with Nintedanib has to be interrupted if any of the criteria listed below are fulfilled:
13Nintedanib Dose Reductions After interruption of Nintedanib the following criteria must be met to restart Nintedanib:GI adverse events: nausea CTCAE grade ≤1-vomiting CTCAE grade 0-diarrhoea CTCAE grade ≤1Liver enzyme elevations: -bilirubin values CTCAE grade 0-AST and ALT CTCAE grade ≤1Neuropathy: neuropathy CTCAE grade ≤2Other non-haematological adverse events:-other non-haematological adverse which are considered drug-related have recovered to less than or equal to the patient's pre-therapy value at trial enrolmentNintedanib - Dose Modification for Toxicity
14Nintedanib Compliance Empty Nintedanib bottles and any remaining medication to be returned at each patient visitPharmacy to perform tablet count (information on handling in IMP manual)Sites will need to have a local process where pharmacy and research staff review patient returns in a timely manner in order to assess patient complianceOver or under compliance should be escalated to the trial teamPatients will be provided with a Nintedanib Diary Card to record their compliancePatients given an alert card to carry for duration of clinical trial
15Detailed information on control arm dosing Protocol lists criteria for:initiation and retreatment - should be assessed for all chemotherapy regimens for each cycle.regimen specific informationdose modification for toxicitydose delaysdose limiting toxicity
17Investigational Medicinal Products - Summary Provided by sponsorNintendanibStore at 15-30oCProvided free of chargeShipped from AlmacFull accountability required usingNiCCC IMP Stock Control Application andNiCCC Master Site Accountability LogHospital own stockPaclitaxelPegylated liposomal doxorubicinTopotecanCarboplatinDoxorubicinAccountability for traceability purposesUse NiCCC Control Arm Accountability logRetain aseptic worksheetsDose banding permitted
18Prescribing Arrangements Study specific prescriptions must be usedSites to develop own prescription. Must include following minimum details in addition to standard prescribing information:clearly identified as NiCCC study. Include Protocol No: /EudraCT NoNiCCC Subject NoElectronic prescriptions can be usedPrescriptions must be version controlled or subject to validation processCopy of final prescription and any updated versions should be retained in the pharmacy file and a copy sent to investigator for insertion into investigator site file.
19Presentation of Nintedanib (BIBF1120) supplies Open label100mg x 30 capsules150mg x 30 capsulesMultilanguage booklet label
20Nintedanib orders and distribution Initial supply is sent automatically to site only when the first patient at site is registered to enter the pre-pathology screen.Pharmacy sites are responsible thereafter for ensuring that sufficient supplies of nintedanib held at siteReplacement supplies must be manually ordered using the NiCCC Resupply Drug Order FormShipped in validated shippers with elpro temperature data logger from AlmacFollow the instructions on the Elpro monitor instruction sheet. PDF files for all shipments must be sent to the BI Elpro Libero Manager Database.Automated response from the BI Elpro Libero Manager Database. Please print and retain in pharmacy site file.
21Nintedanib receiptIf Elpro data logger has alarmed on arrival, quarantine the shipment at correct storage conditions and to and as per instructions in IMP manual. Await written response.If Elpro data logger arrives without an alarm, nintedanib supplies can be used and should be receipted on to the NICCC Master Site Accountability Log and receipted on to the NiCCC IMP Stock Control application.
22Nintedanib dispensing & accountability (1) Individual packs are not allocated, therefore any Med No of correct strength can be used for any patient. However:use lowest available Med No of correct strength first to aid stock rotationAdd investigator and patient IDAdditional dispensing labels may be added as per local practice provided that pre-printed text is not obscured.Accountability is via NICCC IMP stock control application and NICC Master Site Accountability LogHandling information in IMP manual and MSDS available
24Nintedanib patient returns & destruction Sites should have local processes in place to ensure that any potential patient medication compliance issues can be addressed by the local PI or delegate in a timely manner.Sites are permitted to destroy any patient returned study medication once returns documented on the IMP stock control application provided that any discrepancies are resolved.Unused or expired medication can only be destroyed after written permission has been obtained from CR-UK CTU.
25Control IMPs dispensing & accountability Can use dose banded products – see IMP Management and Accountability Manual for requirementsRetain aseptic worksheetsAccountability for traceability purposes recorded on NiCCC Control Arm IMP Accountability LogAdd following text in addition to standard dispensing label:Protocol: NiCCC2013EudraCT No:Principal Investigator: XXXXXXXXPatient ID: XXXXXXXXSponsor: NHS Greater Glasgow and ClydeFor clinical trial use only
26Defects and Temperature Deviations NintedanibQuarantine stock under appropriate temperature conditions ie oCQuarantine stock on NiCCC IMP stock control applicationComplete the NiCCC IMP Temperature Deviation and Defect Report form providing as much detail as possible and to CTCInclude temperature log (temperature excursion) or picture (defect).Telephone if urgent.Control IMPsTemperature deviations, product complaints or recall should be managed as per local site operating procedures
28IMP Stock Control Application (1) Simple, intuitive system to record receipt, dispensing, and destruction.System does not automatically trigger replacement shipments and cannot be used toor order replacement supplies.Self-directed training using current User Guide and Training Guide for NiCCC.Once training completed, ensure that documented on NiCCC Pharmacy Site Training Log and return a copy to CTC.
29IMP Stock Control Application (2) **LIVE** NiCCC IMP stock control application accessed viaSupport: Please in the first instance to report any NiCCC IMP Stock control application problems.Tel: +44 (0)
31Pharmacy Initiation Process Site initiation process - Each member of study team is required to participate in site initiation to ensure compliance with the protocol and training on study procedures. Initiation will be done by site staff accessing on line initiation slides via CR-UK CTU websiteLead pharmacist for the NiCCC will complete Pharmacy Site Assessment Form and return to CR-UK CTUAt a minimum the lead pharmacist must be added on to the site Delegation and Study Specific Training Log. Other pharmacy clinical trial staff may be delegated IMP management responsibilities as per site requirements. These staff will be required to provided evidence of GCP training and current CV’sAcknowledgement sheet must be completed for each member of the study who has viewed the initiation slide presentation to confirm completion.Initiation Accreditation call - Prior to activation of the site a short initiation call will be completed with the main contact for the site.
32Site Set Up CTU GLASGOW SITE INITIATION PROCESS SITE ACTIVATED Main REC approval - MHRA approval - Site Initiation Slides- Investigator File - Pharmacy FileSITEDelegation Log – SSI - R&D Approval- CVs and GCP certificates for PI and Lead Pharmacist - Clinical Trial Agreement - PIS, Consent, GP Letter etc on Trust Headed paper- Lab normal ranges (Haem + Biochem), Accreditation certificates.INITIATION PROCESSSITE ACTIVATEDAutomatic NINTEDANIB shipment triggered by sponsor when 1st patient at site enters pre-pathology screen
34NiCCC – MONITORING UK SITES Central MonitoringTrial sites will be monitored centrally by checking incoming forms for compliance with the protocol, data consistency, missing data and timing. trial staff will be in regular contact with site personnel (by phone/fax/ /letter) to check on progress and deal with any queries that they may have.On-site and Remote Telephone MonitoringThe 1st visit will take the form of a remote telephone monitoring visit when the first patient at site has completed two cycles of treatmentA 2nd telephone monitoring visit will be conducted six months after the randomisation of the 1st patient at siteThe 3rd visit will take the form of an on site monitoring visit 12 months after randomisation of the first patient at a site. The pharmacy department responsible for the trial will be visited to allow monitoring of the pharmacy site file and review of security, storage and accountability of trial drugs.All findings will be discussed at an end of visit and any unresolved issues raised as Action Points.Action Points will be followed up by the monitor until resolved.
35Once site activated Site responsibilities Ensure Pharmacy site file kept up to dateMaintain sufficient quantities of nintedanib 100mg and 150mg packs at siteEnsure NiCCC IMP Stock Control application and accountability logs are kept up to dateInform CR-UK CTU Glasgow of any changes in personnel or arrangements for pharmacyAction amendments where required.Sponsor responsibilitiesForward amendments in a timely mannerReview and amend IMP management process as requiredHelp solve problems & provide support as required.Action Points will be followed up by the monitor until resolved.
36CONTACT DETAILS FOR CRUK CTU Sponsor Clinical Trial Technician Sponsor Clinical Trial PharmacistEliza Valentine Paula MorrisonTel: Tel:Project Manager Clinical Trial CoordinatorClaire Lawless Laura DouglasTel: Tel:Fax: Fax:Pharmacovigilance Manager Pharmacovigilance CTCLindsey Connery Susannah RadfordTel: Tel:Fax: Fax:Clinical Trial Monitor Postal AddressCalum Innes Cancer Research UK Clinical Trials UnitTel: Level 0,Fax: Beatson West of Scotland Cancer CentreMobile : Great Western RoadGlasgow, G12 0YN