A Study Comparing AZD2014 vs Everolimus in Patients With Metastatic Renal Cancer (ZEBRA)
When kidney cancer spreads beyond the kidney, it is known as metastatic kidney cancer. This is very difficult to treat and almost all patients will die of their disease within 2 years of the diagnosis.
Sunitinib and other related drugs (e.g. pazopanib) have become standard therapy for untreated patients with metastatic kidney cancer. They target a growth factor known as VEGF which is important in treating kidney cancer. Although the results with this drug are impressive, patients develop resistance to the drug and stop therapy. It is currently standard practice is to give everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
However the average time to cancer regrowth with everolimus is only 5 months. It is thought this might be because, everolimus only partially inhibits its target (TORC 1 and TORC 2). Therefore further improvement in treating patients is required. AZD2014 is a promising new drug which does inhibit both TORC 1 and TORC 2 and is therefore worthy of investigation in renal cancer as it theoretically could may have advantages over everolimus. Therefore study compares AZD2014 to everolimus in the setting where everolimus is used as standard of care. (e.g. in patients who have failed drug like sunitinib). The study is a randomised trial allowing us to quantify the benefit and potential for further development of AZD2014. Repeat Xrays (CT scans) will be used to assess if the new drug delays tumour growth. Patients will be closely followed up in clinic to ensure safety. A maximum of 122 patients will be recruited into this multi centre national trial. The primary goal of the study is to investigate if AZ2014 delays the time for cancer regrowth (time to progression) compared to everolimus.
Metastatic Clear Cell Renal Carcinoma
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Randomised Phase II Study, Comparing AZD2014 Versus Everolimus With Advanced Metastatic Renal Cancer and Progression on VEGF Targeted Therapy|
- To investigate if single agent AZD2014 delays progression free survival compared to everolimus using RESIST v1.1 [ Time Frame: Completion of study- approx 3 years ] [ Designated as safety issue: No ]
- To evaluate tumour response rate after at least 8 weeks of treatment with the study drugs. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To compare overall survival of the two group of patients. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
AZD2014- tablets, starting dose 50mg BD everyday, until disease progression or untolerable toxicity
AZD2014 vs Everolimus
Other Name: Everolimus/Afinitor
Active Comparator: Everolimus
Everolimus- tablets, starting dose 10mg OD everyday until disease progression or untolerable toxicity
comparing PFS in patients treated with AZD2014 vs Everolimus
Other Name: Afinitor
Renal cell cancer, also referred to as kidney cancer, is diagnosed in approximately 170,000 people worldwide annually, resulting in 82,000 deaths. Treatment for metastatic kidney cancer is difficult. Almost all of the patients die from their disease.
In 2006 a new drug called sunitinib, a tyrosine kinase inhibitor, transformed treatment options. It targets the development of new blood vessels within the cancer. Although the results with this drug are impressive, patients develop resistance a median after 11 months to the drug, relapse and die of renal cancer. It is currently standard practice to switch to everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit.
POTENTIAL RISKS FOR PATIENTS RECEIVING AZD2014:
The main risks and burdens to the patients participating in the study are the potential for side effects of the AZD2014 drug. The phase I study using this drug has been completed, therefore we know it is safe to administer to patients and we have a good idea of what side effects the drug causes. But as the drug is given to larger numbers, additional side effects may be discovered. The activity of the drug has not been evaluated in kidney cancer. Therefore we are not sure if AZD2014 will work
POTENTIAL RISKS FOR PATIENTS RECEIVING EVEROLIMUS:
Everolimus is the current standard therapy for these patients so the risks associated with study drug for these patients are the same as standard of care.
POTENTIAL RISKS FOR ALL PATIENTS:
Side effects will be closely monitored during and after the study. Patients are required to attend clinic weekly for the first four weeks and then every 4 weeks whilst they are on study medication where adverse events will be recorded.
The patient information sheet includes details on expected adverse events for patients to look out for and also details that unexpected events may occur. Patients are provided with the research nurse and principal investigator contact details should any adverse events occur during the course of the study.
Other medical professionals are informed that patients are receiving an experimental drug (through GP letter and labelling of hospital records). There will be an independent data monitoring committee for the trial which will closely assess the side effects of the drugs on a regular basis and the trial results to make sure there are no risk excess to patients.
|Contact: Thomas B Powles||0044 02078828506||Thomas.Powles@bartshealth.nhs.uk|
|Contact: Jack W Bolton, BSc (hons)||email@example.com|
|Royal Bournemouth Hospital||Recruiting|
|Bournemouth, United Kingdom, BH7 7DW|
|Principal Investigator: Tom Geldart|
|Royal Sussex County Hospital||Recruiting|
|Brighton, United Kingdom, BN2 5BE|
|University Hospitals Coventry & Warwickshire NHS Trust||Recruiting|
|Coventry, United Kingdom, CV2 2DX|
|Principal Investigator: Andrew Stockdale|
|Beatson West of Scotland Cancer Center||Recruiting|
|Glasgow, United Kingdom, G12 0YN|
|Principal Investigator: Hilary Glen|
|St. James' Hospital||Recruiting|
|Leeds, United Kingdom, LS9 7TF|
|Principal Investigator: Christy Ralph|
|Barts Health NHS Trust||Recruiting|
|London, United Kingdom, EC1A 6BE|
|Contact: Michelle Greenwood 00442034655054 Michelle.Greenwood@bartshealth.nhs.uk|
|Principal Investigator: Thomas Powles|
|Royal Free London Hospital||Recruiting|
|London, United Kingdom, NW3 2QG|
|Principal Investigator: Ekaterini Boleti|
|Southampton General Hospital||Recruiting|
|Southampton, United Kingdom, SO16 6YD|
|Principal Investigator: Matthew Wheater|
|Southend University Hospital NHS Foundation Trust||Recruiting|
|Westcliff-On-Sea, United Kingdom, SS0 0RY|
|Principal Investigator: Naveed Sarwar|
|Principal Investigator:||Thomas Powles||Queen Mary University of London, UK|