ENSAT registry-based randomized clinical trials for adrenocortical carcinoma

Abstract

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest of the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we therefore provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Adrenocortical Carcinoma in Childhood: A Systematic Review

“…In the pediatric setting, improvement of overall and disease-free survival due to local radiotherapy is known for several tumors, including neuroblastoma [ 171 ]. Over the last few decades, the ENSAT consortium [ 172 , 173 ], which mainly works with adult ACT patients, has shown how centralization and networking can continuously improve patient outcomes, even in rare cancer entities, and should serve as a model for pediatric ACC.…”

The Overall Survival and Progression-Free Survival in Patients with Advanced Adrenocortical Cancer Is Increased after the Multidisciplinary Team Evaluation

“…ACC is a rare malignancy with a poor prognosis and a high risk of recurrence. Systemic therapies have demonstrated low response rates and, currently, there are no standardized treatments for advanced and recurrent forms of ACC due to the lack of randomized and prospective trials [ 19 ]. The rarity and complexity of the disease highlight the need for a multidisciplinary evaluation, including experts in adrenal disease [ 11 , 20 , 21 ].…”

Radiotherapy for pediatric adrenocortical carcinoma – Review of the literature

“…Thus, cooperative groups as established within the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) could be the platform for common randomized trials to further improve patient outcomes in pediatric patients [56,57]. Furthermore, the ENSAT consortium [58,59], which mainly covers adult ACT patients, has shown how centralization and networking can continuously improve patient outcomes, particularly in rare cancer entities. Therefore, it is advisable to encourage a collaboration between the existing groups dedicated to pediatric and adults ACC, aiming for a synergistic action to bring more evidence in the treatment of pACC patients and to improve prognosis and treatment, including a systematic international registry and a common research platform finally leading also to more prospective clinical trials in adolescents.…”