14th July 2022
RAMPART Newsletter - July 2022 Update
The latest RAMPART Newsletter was sent out today. It contains some important updates including; information about the latest protocol amendments for RAMPART and TransRAMPART, CRF updates, Image Repository and the future of RAMPART moving forward.
Links: July Newsletter
24th September 2021
RAMPART Goes Down Under
The RAMPART trial has now officially opened in Australia. The first site open to recruitment is Box Hill Hospital in Melbourne. We expect to open a further 8 sites in the coming months, please refer to the site map for details. We are looking to get more sites in Australia and New Zealand involved in the study. If you are interested in opening the RAMPART at your hospital, please contact the RAMPART team at the University of Sydney (firstname.lastname@example.org) to register your interest.
Links: Site Map
16th September 2021
We're pleased to announce that we have recently published two RAMPART articles in the journal of Contemporary Clinical Trials. The first is focussed on the RAMPART Protocol and describes some of the unique and interesting approaches we are taking to trial conduct. The second paper explores adaptive trial designs, regulatory futureproofing and our experiences in RAMPART.
15th September 2021
New Patient Population Goes Live
We’re pleased to confirm that we are now in a position to start recruiting patients with synchronous ipsilateral adrenal metastases into the RAMPART trial. Thank you for your patience while we made the necessary changes to our trial database. Sites can start screening these patients with immediate effect once RAMPART Protocol v5.0 has received local approval.
22nd July 2021
Recruitment Milestone - 300 Participants!
Our 300th RAMPART participant was recruited this afternoon at Charing Cross Hospital. A massive thank you to all our RAMPART teams for their ongoing support of this important study. Please check out our recruitment table if you'd like to see how you compare to other sites.
There has been a notable increase in recruitment over recent months and we hope to reach the next milestone in record time!
Links: Recruitment Table
22nd July 2021
First French Site
The RAMPART trial has now officially opened in France. The first site open to recruitment is Institut Paoli-Calmettes in Marseille. We plan to open a further 24 sites before the end of the year, please refer to the site map for details.
Links: Site Map
29th June 2021
Protocol Amendment (v5.0 March 2021)
We have now received approval from the MHRA, HRA and REC for an amendment to the RAMPART Protocol (v5.0, Mar-2021)
Changes to the Protocol
There are two main reasons for amending the trial Protocol. Firstly, we are introducing a new patient population into the RAMPART trial. Patients who present with synchronous ipsilateral adrenal metastases, which can be completely resected (adrenal metastasectomy) at the time of nephrectomy, will now be considered eligible for the RAMPART trial. These patients are considered to have a similar risk to those in the high risk group in RAMPART, and are currently treated in the same manner as adjuvant patients. They are an understudied group of patients with a substantial risk of relapse that the RAMPART Trial Management Group (TMG) believe will benefit from adjuvant therapy after surgery. We need to make some minor changes to our trial database to allow these patients to be randomised. We ask that you hold-off screening these patients until you receive further notification from the RAMPART team.
The other main reason for this amendment is a series of changes that aim to reduce the burden on our sites and participants. To achieve this we are implementing remote practices across the study. It is now acceptable to conduct remote pre-treatment assessments, where deemed appropriate by the Investigator. We have also introduced new guidance on the remote consent of potential participants. There are also some substantial changes to the trial assessments. We have removed (ECGs) or reduced the frequency (physical exams, vital signs) of our trial assessments where the TMG felt it was safe to do so.
Updated Supporting Documents
Alongside the updated Protocol, we are also introducing some new and updated supporting documents. The Durvalumab Investigator Brochure (IB) has recently been updated by AstraZeneca and there are new expected toxicities listed for both durvalumab monotherapy and the combination with tremelimumab. It is our intention to use this new version of the IB (v16.0, Oct-2021) as our Reference Safety Information (RSI) moving forward.
In response to the updated safety information we have made some changes to our Participant Information Sheet (PIS) to ensure that our patients are adequately informed. The new version of the PIS (v5.0, Mar-2021) should be given to all prospective patients once local approval has been granted. It is not necessary to re-consent existing participants as the TMG do not feel these updates change the risk/benefit assessment.
We also have a new participation questionnaire, Preferences for Adjuvant Immunotherapy in RAMPART (PAIR), which aims to establish the benefit our participants judge sufficient to make their treatment worthwhile. These questionnaires are optional for RAMPART participants. Those who agree to participate in the Participant Reported Outcome sub-study on the RAMPART Consent Form (optional consent A) should be asked to complete the questionnaire at the relevant visits.
Please note that we have also made some changes to existing CRFs to accommodate the protocol amendments. New versions of the Randomisation CRF (Form01), Eligibility CRF (Form02) and Treatment CRF (Form05) have been attached and should be used with immediate effect. These forms were not part of the substantial amendment submissions and do not require approval for use.
We have prepared a brief set of slides to provide some additional details and guidance about the changes to the RAMPART Protocol and trial practice. These slides should be forwarded to all members of the local research team who are working on the study. Please ensure that the RAMPART Training Log is updated following review of the slides and a copy sent to the RAMPART team email@example.com.
4th February 2021
New Covid-19 CRF and Analysis
There are currently no published prospective data on the safety of Covid-19 vaccines for patients receiving immune checkpoint inhibitor (ICPI) therapy. Thus, there is a need to capture data and understand the impact of ICPIs in modulating the response to the vaccine.
Three Covid-19 vaccines have been approved for use in the UK to date: the Pfizer BioNTec, Oxford University/AstraZeneca and Moderna vaccines. The vaccines are not live vaccines and are therefore acceptable for patients with immunosuppression undergoing cancer treatment. RAMPART trial participants are eligible to receive a Covid-19 vaccine via their registered GPs and we recently contacted sites to provide recommendations for patients about the Covid-19 vaccine. We expect that most RAMPART participants will be vaccinated.
In RAMPART, RCC patients are randomised to receive either active monitoring (no treatment, but observation by clinical and radiological means), durvalumab monotherapy (an anti-PDL-1 therapy), or a combination of durvalumab and tremelimumab (an anti-CTLA-4 therapy). We collect comprehensive data on patient safety. We are therefore in a privileged position where we can prospectively evaluate the safety (and efficacy) of Covid-19 vaccination in patients who are randomised to ICPI therapy or no treatment. We are therefore introducing a new CRF and asking for your help to collect this important data on as many RAMPART patients as possible. The data generated will be relevant to the many patients around the world receiving ICPI therapy and to all patients who will get Covid-19 vaccines in due course.
The new Covid-19 CRF (Form22) has been designed to capture specific information about the vaccinations patients receive and information on subsequent infection. The CRF should be completed once per participant and updated as appropriate. We are very interested to know about any adverse events that are experienced following administration of the vaccines and would ask that you continue to document these on the Adverse Events Log (Form06).
Links: Covid-19 CRF
7th January 2021
First TransRAMPART Site and Participant
Congratulations to the team at Warwick Hospital, who are the first TransRAMPART site to open to recruitment. The team have subsequently also enrolled the first TransRAMPART participant into the study.
24th November 2020
TransRAMPART is a study we are running alongside the main RAMPART trial, which we are delighted to say has been funded by CRUK. We would like to invite all sites participating in the RAMPART to get involved in this important study.
TransRAMPART is an expanded sample collection, building on the samples already obtained through RAMPART and supplementing them with additional sample types and collection time points. The study provides a unique opportunity to address which of our RCC patients are most in need of adjuvant checkpoint inhibitors; predict those patients who will respond to these agents, identify when and how resistance may develop and pre-empt patients who will experience significant toxicity. It is likely that the research conducted on the TransRAMPART samples will lead to tangible benefits for our patients.
To ensure that all sites can contribute to the study, we have defined 3 participation levels (Bronze, Silver and Gold), which increase in complexity. All RAMPART sites are effectively already participating at the Bronze level (single blood samples on recruitment to RAMPART), but with the support of our Investigators we hope that most will commit to collecting the additional samples that will enable us to expand our research. Participating at the Silver level involves relatively little extra effort (longitudinal blood sampling using preservative based tubes, hence no need for processing on-site) and we hope that our ECMC sites will be up to the challenge of participating at the Gold level, which is slightly more involved with some of the samples requiring on-site processing. Please note that there are no additional patient visits required for any of the participation levels – all samples are collected at existing follow-up visits.
As well as contributing to this vital research, there are other benefits to participating at the Silver and Gold levels. The study has been accepted into the NIHR portfolio and so all participants recruited at these levels will be reported on Central Portfolio Management System (CPMS) as a separate entry to the main RAMPART trial.
If your site has interest in participating in the TransRAMPART study please complete the Site Evaluation Form and return a copy to the TransRAMPART team (firstname.lastname@example.org).
23rd November 2020
Recruitment Milestone - 200 Participants!
Our 200th RAMPART participant was recruited this morning at Addenbrooke's Hospital. We would like to thank all our RAMPART sites for your continued support despite all the difficulties presented by the Covid-19 pandemic.
Please check out our recruitment table if you'd like to see how you compare to other sites.
Links: Recruitment Table
| 2nd July 2020
The RAMPART trial has now officially re-opened in the UK. All participating sites will need to complete the re-activation process before they are ready to start recruiting new patients and treating existing patients again. Please contact the RAMPART team if you have not received an email outlining this process.
We have made amendments to the trial protocol in response to the Covid-19 pandemic. The study will now allow extended treatment breaks for the management of patients during the Covid-19 pandemic. There are also new inclusion/exclusion criteria relating to Covid-19.
All trial participants will be offered the opportunity to resume their trial treatment, provided this does not extend beyond one year after their first dose. The local study team will be in contact with all patients to discuss their options.
| 19th March 2020
In the light of the rapidly evolving situation with COVID-19 in the UK, we are implementing a number of amendments to the RAMPART trial with immediate effect. This builds on initial, more general COVID-19 correspondence that was sent on behalf of our unit director on 13th March 2020.
Communication with Patients
Reporting SAEs and Data Collection
Reason for this Amendment
Review of this Amendment