A Study of Anti-PD1 (Nivolumab) Therapy as Pre- and Post-operative Therapy in Metastatic Renal Cell Cancer (ADAPTeR) (ADAPTeR)
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Study of Anti-PD1 (Nivolumab) Therapy as Pre- and Post-operative Therapy in Metastatic Renal Cell Cancer (ADAPTeR)|
- Safety profile of Nivolumab given pre- and post-nephrectomy in metastatic renal cell carcinoma. Safety will be assessed by a summary of adverse events and by the proportion of patients experiencing all grades of toxicity. [ Time Frame: Until disease progression, measured every 2 weeks, on average for 11 months ]
- Response rate [ Time Frame: Until progression or withdrawal of consent, measured every 8 weeks in first year and then every 12 weeks there after, on average for 11 months ]
- Progression free survival [ Time Frame: Until progression or withdrawal of consent, measured every 8 weeks in first year and then every 12 weeks there after, on average for 11 months ]
- Overall survival [ Time Frame: Until death or withdrawal of consent, measured every 12 weeks, on average for 12 months ]
- Changes in biomarkers [ Time Frame: Until progression or withdrawal of consent, at cycle 1, pre-nephrectomy and at disease progression, on average for 11 months ]Changes in biomarkers correlated with both response to treatment and toxicity. This study aims to investigate the relation of ITH and the immune response to RCC in the context of PD-1 checkpoint-blockade, and to correlate putative immune biomarkers with clinical response or resistance in the pre-operative clinical trial 'window' model that has already been established.
|Study Start Date:||April 2015|
|Estimated Study Completion Date:||May 2018|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Nivolumab 3 mg/kg by intravenous infusion, given every two weeks for eight weeks prior to nephrectomy, then post-operatively until patient is no longer deriving clinical benefit
Nivolumab 3 mg/kg by intravenous infusion, given every two weeks for eight weeks prior to nephrectomy, then post-operatively until patient is no longer deriving clinical benefit.
Other Name: Opdivo
Renal cell carcinoma (RCC) is diagnosed in around 8500 patients annually in the UK. Approximately one third of these patients present with metastatic disease where the RCC has spread to other organs. The mainstay of treatment for these patients is systemic drug therapy, but surgery to remove the primary kidney tumour (i.e. nephrectomy) may also provide clinical benefit.
There is no standard preoperative systemic drug therapy in metastatic RCC, but such preoperative therapy is used widely in the treatment of other cancer types. This approach has several potential advantages including shrinking the tumour to help improve surgical outcomes and to aid identification of appropriate postoperative Drug therapy.
Over the last 10 years several agents have demonstrated promising activity in RCC including the monoclonal antibody therapy nivolumab. This novel immunotherapy works by blocking an immune cell receptor (programmed death1(PD1)) which the cancer can otherwise utilise to evade an individuals immune system attack. This study will investigate the use of nivolumab therapy as a preoperative treatment in patients with metastatic RCC for whom nephrectomy is planned. A total of 19 patients will be recruited at the Royal Marsden Hospital Patients will be treated with nivolumab for 8 weeks prior to surgery, after which nivolumab therapy will restart and continue until such time that the patient is not receiving an overall clinical benefit.
The primary aim of the study will be to assess the safety of such a strategy, with further aims to assess clinical effectiveness. This is also a unique opportunity to further investigate the way in which nivolumab works and to identify predictors of treatment response. To achieve this patients will be asked to provide biopsy samples of their RCC pre & post nivolumab treatment and their nephrectomy tissue for research use, alongside additional blood & urine samples.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02446860
|Contact: Chloe McCormackfirstname.lastname@example.org|
|The Royal Marsden NHS Foundation Trust||Recruiting|
|London, United Kingdom, SW36JJ|
|Principal Investigator: James Larkin|
|Principal Investigator:||James Larkin||Royal Marsden NHS Foundation Trust|