A drug strategy targeting stabilised mutant p53 to fight metastatic platinum-resistant ovarian cancer
Coordinator: Nicole CONCIN
Project Number: 602602
EC contribution: € 5,994,072.00
Project website: http://www.gannet53.eu/
Epithelial ovarian cancer (EOC) is the most lethal gyncaecological malignancy causing 41900 deaths annually in Europe. The predominance of aggressive Type II tumours, which are characterised by a high frequency of p53 mutations, and primary or acquired resistance to platinum-based chemotherapy profoundly contribute to the high mortality rate.
With current standard therapy the median overall survival of metastatic platinum-resistant (Pt-R) ovarian cancer patients is only 14 month. There is a pressing need for more effective, innovative treatment strategies to particularly improve survival in this subgroup of EOC patients. The GANNET53 trial aims to achieve this goal by applying a highly innovative concept that has grown from solid basic research findings made by members of the GANNET53 consortium.
This is a drug strategy targeting a central driver of tumour aggressiveness and metastatic ability, namely mutant p53, via an innovative new Hsp90 (heat shock protein 90) inhibition mechanism. The most advanced, second-generation Hsp90 inhibitor will be used, Ganetespib. The first part (Phase I) of the GANNET53 trial will test the safety of Ganetespib in a new combination with standard chemotherapy (Paclitaxel weekly) in Pt-R Type II EOC patients. The second part (randomised Phase II) will examine the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone in EOC patients with Pt-R Type II tumours.
We established a highly efficient consortium with previously proven capability and manpower to perform this multicentre clinical trial and assess our innovative therapeutic concept in this deadly disease. Our consortium consists of national clinical trial groups in gynaecological oncology and high-volume University centres as well as noted p53 scientists and 3 innovative SMEs. Since ovarian cancer is defined as a rare cancer a scale at the European level is crucial for the planned clinical trial.