Study B021990 (AVAglio) (ongoing) Wound healing complications To investigate the efficacy and safety of bevacizumab, temozolomide and radiotherapy followed by 6 cycles maintenance with bevacizumab and temozolomide as compared to placebo, temozolomide, and radiotherapy followed by 6 cycles maintenance with placebo and temozolomide. CSR 2013 (Submitted as part of this filing) Study NSABP C-08 (ongoing) Wound healing complications (Note: the pharmacovigilance plan does not assign other safety concerns to this study, however the RMP does assign other risks to this study. Study title: Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Colon Cancer. Objectives: to characterise the comparative incidence of delayed vascular events in bevacizumabtreated patients following the discontinuation of bevacizumab and in concurrently enrolled control patients. Estimated study end 2014. Final report due 2015. BO20924 BERNIE) (ongoing) Physeal dysokasia: Clinical significance in paediatric patients Long-term effects of bevacizumab when used in the paediatric population. open-label, multi-centre, randomised Phase II trial in children and adolescents with metastatic rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma to assess addition of bevacizumab to chemotherapy CSR expected first quarter 2016. Final report due first quarter 2017 CSR=company study report; DSMBs=Data and Safety Monitoring Board Risk minimisation activities Routine risk minimisation activities are proposed for all safety concerns except for one area of missing information ‘safety profile of the different treatment combination in patients with non-squamous NSCLC’. It is recommended that the ASA be revised to comply with the standard format specified in the TGA RMP Questions and Answers. This includes information on Australian specific epidemiological data. Furthermore, the sponsor should include the following within the ASA:
The conversion to the new EU RMP template also lead to deletion of the following text: Potential for Overdose. Epidemiology of the target population unexposed to the product. Epidemiology of safety concerns in target population. Table of study exclusion criteria. Projection post-authorisation usage. Update to the RMP For the safety concern of ‘congestive heart failure’ the sponsor makes the following statement regarding additional pharmacovigilance: ‘Safety monitoring plan implemented in ongoing/planned breast cancer studies sequential regular LVEF monitoring in breast cancer studies cardiology expert in DSMBs guided questionnaire’. It is recommended that the sponsor clarify exactly what studies they are referring to, the study titles, milestones and submit protocols for any planned studies to the TGA for review. The list of breast cancer studies with sequential regular LVEF monitoring, cardiology expert in DSMB and CHF guided questionnaires are listed below. Protocols for these studies have been enclosed in module 2.7.6. BO20289 (BEATRICE) Title: An international multi-centre open-label 2-arm Phase III of adjuvant bevacizumab in ‘triple negative’ breast cancer. Milestone: Primary analysis completed July 2012, patients on follow up for OS analysis BO20906/AVF4285s (BETH) study: Title: A Multicenter Phase III Randomized of Adjuvant Therapy for Patients with Node-Positive or High Risk Breast Cancer Comparing Chemotherapy Plus Trastuzumab with Chemotherapy Plus Trastuzumab Plus Bevacizumab Milestone: Ongoing – Primary analysis planned Q4 2013 BO20231 (AVEREL) study: Title: A randomized, open-label, 2-arm, multicentre, Phase III study to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab/docetaxel compared with trastuzumab/docetaxel alone as first line treatment for patients with HER2 positive locally recurrent or metastatic breast cancer. Milestone: Primary analysis completed October 2011, end of study planned first quarter 2014 This is acceptable. It is recommended that the sponsor include the titles of these studies within the pharmacovigilance plan in the RMP and ASA.
Professional’ letter in Australia regarding the risk of necrotizing fasciitis. This letter states changes to the product information regarding this risk. The proposed PI submitted with the current application however does not contain this statement. The sponsor should update the proposed PI accordingly. has been included in the revised draft PI provided with this response. In regard to the proposed routine risk minimisation activities, it is recommended to the Delegate that the draft consumer medicine information document be revised to reflect any changes made to the proposed Australian PI. Roche acknowledge that the draft consumer medicine information be revised to reflect any changes made to the proposed Australian PI. This is acceptable. In regards to the ASA: a) It is recommended that the ASA be revised to comply with the standard format specified in the TGA RMP Q&A’s. ASA Version 4.0, November 2013, has been revised to comply with the standard format specified in the TGA RMP Q&A’s. ASA Version 4.0 will be submitted to TGA on 7 November 2013. This is acceptable. 9. b) The studies referenced in the pharmacovigilance plan will generate safety data that will simply support the known safety profile of the medicine, while others will generate data that will provoke applications to amend the Australian registration details. To this end, it is suggested that the sponsor should provide an attachment to the ASA setting out all the forthcoming studies and the anticipated dates for Roche acknowledge the recommendation. Following assessment of the data generated from studies referenced in the pharmacovigilance plan, the company Core Data Sheet and Australian PI will be revised accordingly. This recommendation refers to the ASA and not to the Core Data or the Australian PI. To clarify, It is recommended that the next update of the ASA contain a table stating all ongoing and planned studies with milestones and the anticipated dates for their submission in Australia.