PRISM
Research type
Research Study
Full title
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
IRAS ID
218853
Contact name
Naveen Vasudev
Contact email
Sponsor organisation
University of Leeds
Eudract number
2017-001476-33
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Research Summary:
The overall aim of the study is to determine whether alternative scheduling of ipilimumab, when given in combination with nivolumab, is associated with a favourable toxicity profile and sufficient activity to warrant further investigation, with additional evaluation of potential benefits in terms of discontinuation rates and quality of life (QoL), in patients with metastatic renal cell carcinoma (mRCC).
Previously untreated patients with metastatic clear cell renal cell carcinoma, fit enough to receive treatment with combination ipilumumab and nivolumab, will form the study population.The primary objective is to assess whether the proposed alternative scheduling of ipilimumab indicates potential for further investigation in terms of safety and efficacy, as defined by the the proportion of patients who experience a grade 3/4 adverse reaction within 12 months of starting trial treatment and the 12 month progression-free survival. Secondary objectives include discontinuation rates, overall response rates, overall survival rates and health related quality of life. Exploratory objectives include exploration of circulating and tissue-based predictive biomarkers of response.
The trial will provide a comparison of how well the treatment is tolerated between the alternative scheduling (12 weekly) and standard scheduling (3 weekly). The trial will also provide supportive data comparing our results from the alternative scheduling of the trial treatment to historical control data with sunitinib (a standard treatment for renal cell carcinoma). To warrant further investigation, the alternative schedule must show potential in terms of both safety and efficacy.
Summary of results:
Standard treatment for advanced kidney cancer includes the use of immunotherapy. This is a type of treatment which works by stimulating the body’s own immune system to fight against cancer cells.
Clinical trials have shown that giving two immunotherapy drugs (nivolumab and ipilimumab) together is an effective initial treatment for many patients with advanced kidney cancer. However, using both drugs together is known to cause more side effects than using the drugs by themselves. These side effects can sometimes be unpleasant and/or serious, and may even mean that treatment needs to be stopped early.
The PRISM trial explored whether giving one of the drugs (ipilimumab) less often but over a longer time period (i.e. receiving the same amount of drug in total), would result in fewer side effects, while still working as well as when given in the standard way. The standard schedule is to give the drug every three weeks for four doses. In the modified schedule, the drug was given every 12 weeks for four doses.
Patients with untreated, advanced kidney cancer were invited to take part in the study, which involved 15 hospitals across the UK. 195patients took part, with two thirds of participants randomly allocated to the modified ipilimumab schedule (every 12 weeks).
The proportion of patients who experienced serious side-effects during treatment dropped by 20% when the treatment was spaced out (33% for the modified schedule compared to 53% for the standard schedule).
Also, fewer patients had to stop treatment due to side-effects when the ipilimumab was given every 12 weeks. Overall, 23% of patients receiving the modified schedule stopped therapy due to treatment-related side-effects, compared to 39% in patients receiving the standard schedule.
Whilst leaving longer between each dose of treatment can lead to concerns about loss of activity, the results from the trial did not suggest any obvious differences in how well the treatment worked when giving ipilimumab less often. How long patients lived and the amount of tumour shrinkage looked similar in both groups, but due to the size of the study, the trial could not definitively prove this.
The results of this phase II study showed that spacing out the treatment over a longer period produces fewer side effects without reducing the effect of the treatment. This suggests that it may be possible to improve how well tolerated immunotherapy drugs are, without compromising how well they work, in patients with advanced kidney cancer.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
17/YH/0187
Date of REC Opinion
14 Jun 2017
REC opinion
Favourable Opinion