EORTC precision medicine study brings therapeutic progress to patients with very rare cancers

Treatment of papillary renal cell carcinoma (pRCC) remains empiric.  With an incidence of less than 5% among all kidney cancers  pRCC qualifies for orphan disease and remains therefore poorly known and benefits from fewer treatments with limited activity.

Building on its track records for rare entities and implementing new methodologies for so called “basket clinical studies” addressing different tumor types documented to be driven by the same molecular alterations in the same protocol, the EORTC has launched the CREATE study under the leadership of Professor Patrick Schöffski (Leuven, Belgium).

The EORTC CREATE study aims at assessing the activity and safety of Crizotinib in 6 independent tumor types including advanced papillary renal cell carcinoma type 1 (pRCC1), a very rare and frequently misdiagnosed cancer type. This trial is supported by Pfizer Inc. and the pRCC1 cohort of the study has been reported at the American Association for Cancer Research annual congress on Sunday Apr 17, 2016 (Permanent Abstract Number: CT006)

Between December 2012 and January 2016, 13 high-volume sites in 8 countries recruited 41 patients with local diagnosis of pRCC1, of whom only 23 had a centrally confirmed diagnosis of pRCC1 and were treated with Crizotinib.

The study, with real time reference pathology and molecular characterization showed that 17% of patients with confirmed pRCC1 had MET mutations in exons 16-19 (MET +) and 8% were found with MET amplifications.

Among 4 patients with mutations in these exons, 2 patients achieved a confirmed partial response and one had stable disease; all 3 had long lasting disease control (≥ 14 treatment cycles). The data also suggest that rarer patients with MET amplifications may achieve similar outcome irrespective of MET mutation in exons 16-19. By contrast, disease stabilization in patients without a detected somatic mutation in exon 16-19 was generally short and they did not achieve objective responses

With 2 out of only 4 MET+ pRCC1 patients achieving a confirmed partial response, Crizotinib did meet the stage 1 success criteria of the Simon’s optimal two stage design foreseen in the study. However, the low incidence of reference-pathology proven MET+ pRCC1 precludes completion of stage 2 in optimal timing.

Professor P. Schöffski (photo) points out that: “The findings of this study offers a new treatment option for papillary renal cell carcinoma type 1 with MET mutation or amplification, an unaddressed patient population demonstrating the feasibility of precision medicine clinical trials in patient groups which remain under served. The CREATE study continues for other rare tumor types and will surely position as a landmark in the field of oncology for rare tumors”.

Dr Laurence Collette, head of the statistical departments at the EORTC emphasizes that “ This achievement highlights the role of academic groups best placed to address specific public health questions. In addition, contribution of the academic sector in positioning new treatments is valued and of specific importance here as EORTC acknowledges the partnership with the pharmaceutical industry sector supporting such initiative”

Dr Sandrine Marreaud and Sandra Collette, respectively clinical trial physician and clinical research statistician in charge of this project at the EORTC Headquarters alert that “there is a need to stimulate methodological research for orphan diseases as well as to rapidly address the European regulatory mechanisms to facilitate translational and clinical research for rare cancers. For the sake of equal opportunities, there is no reason why rare cancer patients would not benefit of methodologically robust studies, like frequent disease patients do”.


The European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration. Both multinational and multidisciplinary, the EORTC Network comprises more than 4,500 collaborators from all disciplines involved in cancer treatment and research in more than 600 hospitals in over 30 countries. Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices. EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run.

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