Clinical Trial: 1st-line Activity of Dovitinib and Correlation With Genetic Changes in RCC

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Dovitinib In 1st-Line Renal Cell Carcinoma, an Investigation Into Tumour GENe Status and Correlation With Efficacy - 1st Exploratory Study

Brief Summary:

The main purpose of this study is to find out how useful dovitinib is when given as the initial treatment to participants with advanced kidney cancer, that has spread to other parts of the body. The usefulness of dovitinib will be assessed by: how long the disease is controlled while participants are receiving the drug, the proportion of participants who get a reduction in the size of their tumours and how long participants live (both while on dovitinib and on any subsequent therapy they may receive).

If participants have secondary disease in the bones, the study will evaluate how useful dovitinib is in controlling this site of disease. In addition, this study will look for changes in the genetic makeup of tumour cells and see if some of these changes are associated with a benefit from dovitinib. The study will also compare and contrast the genetic changes in the primary tumour cells with cells from secondary tumour specimens, and with cells from tumour specimens taken if a participant's disease has worsened. The purpose of the latter is to identify possible ways in which the tumour becomes resistant to the study drug.

Detailed Summary:

The purpose of this prospective, single centre, non-randomised, open-label, phase II study will evaluate the activity of dovitinib in the treatment naïve population of patients with advanced RCC.

Background: Prior to the middle of last decade, the only systemic therapy for patients with advanced RCC was immunotherapy (interleukin-2 and interferon-alpha) with limited effectiveness and a multitude of side-effects. Since 2006, there have been 6 targeted therapies that have been FDA-registered for the treatment of advanced RCC; the anti-VEGFR tyrosine kinase inhibitors (sunitinib, sorafenib and pazopanib), the anti-VEGF antibody bevacizumab (with interferon-alpha) and the mTOR inhibitors (everolimus and temsirolimus). These treatments have significantly advanced outcomes for patients with this disease but unfortunately they do not represent cures. The median overall survival for patients treated with a standard first-line therapy (sunitinib) is just over 2 years and the median PFS for subjects receiving this agent is only 11 months. This means that the typical time it takes for subjects to develop resistance to standard first-line tyrosine kinase inhibitor (TKI) treatment, as evidenced by significant tumour growth on imaging, is under 1 year.

Despite the recent rapid advancements in the treatment options for subjects with advanced RCC, there is still an unmet need for more effective therapeutic options for patients with this disease so as to improve survival and make steps towards the ultimate treatment aim for patients with metastatic disease - cure. Available data suggests that dovitinib is a very active agent in metastatic RCC. If it has efficacy in the heavily pre-treated RCC population, one would expect it to be considerably more active when it is moved forward into the first-line setting.

Description: Subjects will undergo baseline radiology assessment with a CT scan of the chest, abdomen, pelvis and head within 4 weeks of registration. Thereafter subjects will then undergo CT scans of the chest, abdomen and pelvis (where possible using the same technique) every 9 weeks until week 54. From week 54 onward, subjects will undergo CT scans of the chest, abdomen and pelvis every 12 weeks until disease progression. Tumour responses will be evaluated using RECIST 1.1. Confirmation of responses (PR/CR) with repeat CT is not required as the primary end-point is PFS. CT will be the only imaging modality required for subjects on study. The RECIST 1.1 assessments will be done in Auckland by one of the members of the Tumour Response EvAluation Team (TREAT) who have expertise in RECIST reporting.