RAMPART Re-Opens

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.

COVID-19 Update

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 13^th March 2020.

Recruitment

• Participant accrual to RAMPART is suspended
• This includes all patients who have been screened or who have already provided consent to participate
• No further screening or pre-treatment visits are required

Treatment

• Trial treatment for all participants is also suspended
• This includes participants who have been randomised, but have not yet commenced treatment

Follow-up

• The need for clinic visits for trial follow-up should be assessed on an individual participant basis, and should be at the discretion of the patient’s treating clinician
• Follow-up to ensure participant safety and to manage developing side-effects of treatment already received should be prioritised
• We advise clinicians to assess the risk for individual participants of travel to, and attendance at hospital for protocol-mandated imaging and clinical assessment and adapt the schedule as they feel appropriate
• Telephone follow-up in place of clinic visits is acceptable where possible and safe

Communication with Patients

• Please communicate these changes with the patients at your site at your earliest convenience. We have produced a letter which you can share with participants. We hope this will help. Our Research Ethics Committee have confirmed the letter can be given to participants without any further approvals.

Reporting SAEs and Data Collection

• Please continue to report any SAEs as per the usual reporting route, faxing the SAE CRF to 0207 670 4818. A member of the team will confirm receipt of the SAE form.
• Please send CRFs via galaxkey as we are currently unable to process any CRFs received by post. If you do not have a galaxkey account, let us know and we can create one for you.
• Depending on the follow-up participants at your site receive in the coming months we can advise you on the CRFs that you should complete

Reason for this Amendment

• Patients receiving checkpoint inhibitor treatments are susceptible to developing side effects that require the use of steroids. Steroids are likely to expose patients to an unacceptable added risk of COVID-19 related morbidity and mortality
• For participants already on the study, bringing them to hospital for treatment or study related visits exposes them to a risk of COVID-19, which they otherwise might not have had
• With rising COVID-19 infection these risks outweighs the uncertain benefit of adjuvant treatment

Review of this Amendment

• We will review all of these decisions on a regular basis and will notify you of any changes 

Practicalities

• The MRHA have confirmed that these changes to RAMPART can be implemented without a substantial amendment. We have also informed the Research Ethics Committee and AstraZeneca
• Please file a copy of this correspondence in your Investigator Site File
• Please inform your R&D department of these amendments and advise them to contact us if they need further information

Contacting Us

• In line with government advice, all MRC CTU staff are working from home where possible. We have diverted our work telephone numbers, so you can reach any member of the trial team using the telephone numbers listed in the protocol
• You can also email the trial inbox: mrcctu.rampart@ucl.ac.uk
• We will forward clinical questions to the Chief Investigator or Clinical Reviewer for advice as necessary
• We will continue to post relevant information on our trial website: www.rampart-trial.org

16^th September 2021

New Publications

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.

Links: Protocol Paper, Design Rationale Paper

15^th 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.

22^nd July 2021

Recruitment Milestone - 300 Participants!

Our 300^th 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

22^nd 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

29^th 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.

Training

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 mrcctu.rampart@ucl.ac.uk.

Links: Amendment Documents, Randomisation CRF, Eligibility CRF, Treatment CRF, Training Slides

 4^th 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

7^th 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.