Metastatic Clear Cell Renal Cancer Clinical Trial
Official title:
A Phase I Study Investigating Everolimus and Dovitinib in Metastatic Clear Cell Renal Cancer
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.
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.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
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| Active, not recruiting |
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