Spots Global Cancer Trial Database for Dose Escalation Study Investigating Everolimus and Dovitinib in Metastatic Clear Cell Renal Cancer

Study Description

Brief Summary: 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 3 years. Sunitinib has become standard therapy for untreated patients with metastatic clear cell renal (kidney) cancer. It targets a growth factor known as VEGF which is important in treating renal cancer. Although the results with this drug are impressive, patients develop resistance to the drug, relapse and die of renal cancer. It is currently standard practice is to treat patients with everolimus when resistance to sunitinib occurs; this is associated with clear clinical benefit. However the median time to progression with everolimus is 4.9 months in previously treated patients, therefore further improvement in treating patients is required. The optimal way of achieving this is to increase the efficacy of everolimus by adding agents which directly target the cause of resistance to sunitinib. Dovitinib is a promising new drug in renal cancer. Dovitinib blocks cellular functions such as activation of downstream signalling molecules, cell proliferation and survival. Combining dovitinib and everolimus is very attractive. This trial is aimed to establish the maximum tolerated dose for the combination of dovitinib and everolimus in clear call renal cancer, which can then be taken into a randomised phase II study. A maximum of 30 patients will be recruited into this multi centre national trial. Expansion Cohort: The study has established the MAD and the MTD. The MTD was Cohort 0 (Everolimus 5mg and Dovitinib 200mg). 6 patients were recruited in this cohort with only 1 patient experiencing a DLT. A further 3 patients were recruited into Cohort 1 (Everolimus 5mg and Dovitinib 300mg), where 2 patients experienced a DLT. A total of 7 assessable patients will be recruited during the expansion phase at the MTD (Cohort 0: Everolimus 5mg and Dovitinib 200mg) to further define the safety, tolerability, efficacy, PK and biological end points. Assessable patients for the expansion cohort are defined as being on the study for a minimum of 6 weeks. Any patients enrolled who are not assessable will be replaced.

Detailed Description: 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. However the median time to progression with everolimus is 4 months in previously treated patients, therefore further improvement in treating patients is required. The optimal way of achieving this is to increase the efficacy of everolimus by adding agents which directly target the cause of resistance to sunitinib. dovitnib is a promising new drug the pharmacology data from a variety of in vitro and in vivo studies with dovitnib provided preclinical rationale for clinical evaluation of dovitinib in patients with metastatic clear cell renal cancer. The combination of everolimus with dovitnib will target 3 major protagonists associated with tumour growth The main risks and burdens to the patients participating in the study are the potential for side effects of the trial medicines, these two drugs have not been used in combination together and although there is safety data on each drug, there is no known safety data on the drugs when used in combination. The first cohort of patients will receive 200mg of dovitnib and 5mg of everolimus. In previous studies these drugs have been administered separately and at higher doses. The maximum tolerated dose (MTD) of dovitnib for the 5-day on/ 2-day off dosing schedule has been defined as 500mg/day in a previous Phase I studies. In the RECORD-1 study (a Phase III double blind randomised trial investigating everolimus) a dose of 10mg was used. Cohorts of three patients will be treated in each dose level. A minimum of 14 days will elapse between the first patient being treated in each cohort and entering the next patient. Further patients may be entered concurrently. Toxicity will be assessed according to NCI CTCAE v4.0; if no dose limiting toxicity (DLT) occurs dose escalation will be undertaken for the next cohort of patients. In the event of DLT in 1out of the 3 patients the cohort will be expanded to a maximum of 6 patients. If more than or equal to 2 out of 6 patients experience DLT dose escalation will be halted and the maximum administered dose (MAD) has been reached. If less than or equal to 1 out of 6 patients had DLT dose escalation may continue. Patients may not personally benefit from being in this study. However the information we gain from this study might help to treat future patients who have metastatic kidney cancer.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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