PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma
| العنوان: | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
|---|---|
| المؤلفون: | Louise Flanagan, Paul Nathan, Sarah Brown, Rosamonde E. Banks, Geraldine Murden, Tom Waddell, Kate Fife, Thomas Powles, Hannah Buckley, James Larkin, Heather Poad, Fiona Collinson, Eszter Katona, Joanne Brown, Galina Velikova, Naveen S. Vasudev, Gemma Ainsworth, Helen Howard |
| المصدر: | BMC Cancer BMC Cancer, Vol 19, Iss 1, Pp 1-9 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Male, Cancer Research, Programmed Cell Death 1 Receptor, Randomised, Trial, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Renal cell carcinoma, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, CTLA-4 Antigen, 030212 general & internal medicine, Neoplasm Metastasis, education.field_of_study, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Nivolumab, Treatment Outcome, Renal cancer, Schedule, 030220 oncology & carcinogenesis, Female, Immunotherapy, Safety, medicine.drug, Adult, medicine.medical_specialty, Efficacy, Population, Ipilimumab, lcsh:RC254-282, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, Genetics, Humans, Progression-free survival, education, Carcinoma, Renal Cell, Aged, business.industry, medicine.disease, Discontinuation, Quality of Life, business |
| الوصف: | Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing. |
| وصف الملف: | application/pdf |
| تدمد: | 1471-2407 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9547f1c60334675221047be28971ffb7Test https://pubmed.ncbi.nlm.nih.gov/31727024Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9547f1c60334675221047be28971ffb7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 |
|---|