Periodic Reporting for period 1 - DE-ESCALATE (INTERMITTENT ANDROGEN DEPRIVATION THERAPY IN THE ERA OF ANDROGEN RECEPTOR PATHWAY INHIBITORS; A PHASE 3 PRAGMATIC RANDOMISED TRIAL)
Reporting period: 2023-06-01 to 2024-05-31
Prostate Cancer is the most common cancer in European men. Despite dramatic improvements in early diagnostic and local treatment, one out of five prostate cancer patients will die from their disease. Despite progress in the past years, it remains critical to improve on the present strategy for advanced and metastatic prostate cancer. Within the proposed project, we will evaluate whether intermittent androgen deprivation treatment (iADT) in metastatic prostate cancer is not inferior to continuous treatment in terms of oncological benefit while minimizing side effects and resource utilization and improving patient quality of life. The proposed clinical trial is designed to detect early if iADT has a negative impact on overall survival compared to continuous therapy. If successful, the outcomes of the project will define a new evidence-based standard of care for metastatic hormone sensitive prostate cancer. The proposed research could lead to improved patient survival and quality of life but also improve health system sustainability. This is a multidisciplinary and multistakeholder consortium involving clinical oncologists, surgeons, health economists and patient representatives. The study design was successfully discussed with patients.
The clinical trial protocol was developed collaboratively with all partners, including the patient representative EUO. Understanding that a treatment de-escalation pragmatic trial is not a usual type of study design, we proactively consulted regulatory authorities via the Simultaneous National Scientific Advice (SNSA) mechanism before submitting the trial for approval under the Clinical trial Regulation (CTR). In its feedback, SNSA challenged several key aspects of the clinical trial design overlooking the fact that all involved drugs are standard of care and intermittent treatment is a common clinical practice. This clinical trial does not expose patients to additional risks. EORTC subsequently consulted with EMA, DG RTD and DG Health to address these issues. We adapted the protocol to clarify certain aspects and submitted it for authorization under the CTR in February 2024.
As of May 2024, we received a total of 228 queries (Requests for Information (RFI’s)) challenging key aspects of the protocol as approved by Horizon Europe evaluators. It became clear that obtaining clinical trial approval was unfeasible because it was impossible to address evaluators’ requests and submit a new protocol version within the given deadline. Furthermore, implementing several requests would have significantly altered the study design approved by Horizon Europe evaluators. In May 2024, we decided to withdraw the protocol submission under the CTR and to fully assess the situation and explore possible solutions. EORTC engaged the EMA which agreed to support discussion between EORTC and the Heads of Medicines Agencies Clinical Trials Coordination group to find a resolution. Meanwhile, CTI assisted EORTC in initiating direct communication with Irish competent authority HPRA, the reference member state for the CTR process. The preliminary outcomes are encouraging, with DE-ESCALATE being recognised as an important study by regulators. This treatment de-escalation pragmatic trial is the first of its kind to be assessed under the CTR, highlighting a learning curve and the need for better communication to resolve misunderstandings from both sides. The EORTC will adapt the protocol to clarify several aspects as requested by regulators and plans to resubmit the protocol to the CTR in October 2024 after full clarification and alignment with regulators.On the health economics side, activities commenced as planned at the project start, despite uncertainties surrounding the approval of the study protocol. Explorative work was conducted, and input from clinical experts was collected, resulting in the conceptual value framework submitted as the first deliverable from this work. Regarding communication and dissemination, the project website, social media platforms and newsletters were launched. The Plan for Dissemination and Exploitation deliverable was prepared. However, active communication is on hold until the clinical trial is accepted.In conclusion, the project is on hold as the consortium seeks to identify a path forward to conduct the clinical trial in accordance with the study design outlined in the grant agreement. It should be emphasised that the issue is not related to the capacity of the consortium to fulfil its commitments but rather a general problem associated with the implementation of the CTR and the unique design of the DE-ESCALATE clinical trial. This situation will impact project timelines.
As of May 2024, we received a total of 228 queries (Requests for Information (RFI’s)) challenging key aspects of the protocol as approved by Horizon Europe evaluators. It became clear that obtaining clinical trial approval was unfeasible because it was impossible to address evaluators’ requests and submit a new protocol version within the given deadline. Furthermore, implementing several requests would have significantly altered the study design approved by Horizon Europe evaluators. In May 2024, we decided to withdraw the protocol submission under the CTR and to fully assess the situation and explore possible solutions. EORTC engaged the EMA which agreed to support discussion between EORTC and the Heads of Medicines Agencies Clinical Trials Coordination group to find a resolution. Meanwhile, CTI assisted EORTC in initiating direct communication with Irish competent authority HPRA, the reference member state for the CTR process. The preliminary outcomes are encouraging, with DE-ESCALATE being recognised as an important study by regulators. This treatment de-escalation pragmatic trial is the first of its kind to be assessed under the CTR, highlighting a learning curve and the need for better communication to resolve misunderstandings from both sides. The EORTC will adapt the protocol to clarify several aspects as requested by regulators and plans to resubmit the protocol to the CTR in October 2024 after full clarification and alignment with regulators.On the health economics side, activities commenced as planned at the project start, despite uncertainties surrounding the approval of the study protocol. Explorative work was conducted, and input from clinical experts was collected, resulting in the conceptual value framework submitted as the first deliverable from this work. Regarding communication and dissemination, the project website, social media platforms and newsletters were launched. The Plan for Dissemination and Exploitation deliverable was prepared. However, active communication is on hold until the clinical trial is accepted.In conclusion, the project is on hold as the consortium seeks to identify a path forward to conduct the clinical trial in accordance with the study design outlined in the grant agreement. It should be emphasised that the issue is not related to the capacity of the consortium to fulfil its commitments but rather a general problem associated with the implementation of the CTR and the unique design of the DE-ESCALATE clinical trial. This situation will impact project timelines.
It is too early. The project clinical trial has not started yet.