MK-3475 in the treatment of Advanced/Metastatic Urothelial Carcinoma
Research type
Research Study
Full title
A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab with or without Platinum-Based Combination Chemotherapy versus Chemotherapy in Subjects with Advanced or Metastatic Urothelial Carcinoma
IRAS ID
212844
Contact name
Thomas Powles
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2015-005731-41
Duration of Study in the UK
3 years, 8 months, 1 days
Research summary
Urothelial (transitional cell) carcinoma describes a range of tumours that arise from the urothelial endothelium, which includes the bladder, renal pelvis, ureter and urethra. Over 300,000 cases of urothelial carcinoma occur annually, making this the seventh most common cancer worldwide. Urothelial carcinoma (as distinct from squamous cell or adenocarcinoma) is the main type of bladder cancer in the United States and Western Europe, where it accounts for approximately 90% of bladder cancers. A variety of cancer medicines (chemotherapy) can be used, however the outcome is poor in advanced or spreading (metastatic) cancers.
This phase III study will determine the efficacy and safety of pembrolizumab with or without chemotherapy versus chemotherapy alone in subjects with advanced or metastatic urothelial carcinoma (bladder cancer). The chemotherapy used in this study are Cisplatin or Carboplatin with Gemcitabine.
Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells come upon cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2 which are proteins on the surface of cancer cells. The activated immune cells become exhausted or die thus stopping them from attacking the cancer. The study drug, pembrolizumab, has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
Approximately 990 men and women aged 18 years and above with advanced/metastatic urothelial cancer will receive treatment for up to 24 months (36 months if they undergo re-treatment phase). Patients will be randomised between three arms of the study (pembrolizumab alone, pembrolizumab with chemotherapy, chemotherapy alone). Prior to enrolling, patients will provide a tumour tissue sample, which will be tested for certain cancer markers.
The study is funded by Merck Sharp & Dohme Limited and will take place at 6 study centres in the UK.REC name
London - London Bridge Research Ethics Committee
REC reference
16/LO/1697
Date of REC Opinion
4 Nov 2016
REC opinion
Further Information Favourable Opinion