Phase I/II Trial of RAD001 Plus Nexavar in Patients With Kidney Cancer
The purpose of this study is to see whether the combination for RAD001 and Nexavar® works better when given together than they do alone. The purpose of the first phase of this study is to determine the best dose of RAD001 given with Nexavar®, and to see what effects, good and/or bad, the study drug has on the subject and the subject's tumor. This study will also observe side effects experienced by the subject.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of RAD001 Plus Nexavar® For Patients With Metastatic Renal Cell Carcinoma|
- Phase I: To establish the maximally tolerated dose (MTD) and safety profile of RAD001 in combination with Nexavar® in patients with metastatic renal cell carcinoma (MRCC). [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Phase II: Study the anti-tumor effects of RAD001 plus Nexavar® [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Phase II: Response rate [ Time Frame: restaging every 8 weeks ] [ Designated as safety issue: No ]
- Duration of tumor response [ Time Frame: restaging every 8 weeks ] [ Designated as safety issue: No ]
- Progression free survival [ Time Frame: restaging every 8 weeks ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: restaging every 8 weeks ] [ Designated as safety issue: No ]
- Study the safety of RAD001 plus Nexavar® given at MTD. [ Time Frame: AEs as occur ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2006|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
To establish the maximally tolerated dose (MTD) of RAD001 in combination with Nexavar®
RAD001 will be administered orally once a day, daily, without interruption per 4 wk cycle for 2 cycles. MTD is established in Phase I portion of trial (2.5, 5 or 10mg). If responding, additional therapy will be given.
Other Name: EverolimusDrug: Sorafenib
A dose of 400mg of Nexavar® will be administered orally twice a day, daily, without an interruption per 4 week cycle for 2 cycles. If responding, additional therapy will be given.
Other Name: Nexavar®, BAY-4900
Despite significant progress in understanding the biology of renal cell carcinoma (RCC), it is estimated that over 35, 000 people in the United States will be diagnosed and approximately 12, 000 have died from this disease in 2005. Renal cell carcinoma presently ranks tenth as the leading cause of cancer death and constitutes 3% of all solid neoplasms.
In contrast to many other malignancies, treatment for RCC is limited. Treatment remains a highly difficult and perplexing challenge due to its resistance to both chemotherapy and hormone therapy and limited response to cytokines. Despite recent advances in our fundamental knowledge of RCC biology and development of molecular therapeutics, more clinical research will be required to best guide our use of these exciting new agents in combination regimens.
The combination of RAD001 and Nexavar®, in current clinical trials with minimal toxicity, represents a treatment regimen which should be investigated for tolerance and toxicity as well as initial phase II efficacy. The study is designed to evaluate the MTD. Following the completion of the phase I, utilizing the MTD, Phase II study is designed to evaluate the anti-tumor activity.
|United States, Texas|
|The Methodist Hospital Research Institute|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert J Amato, DO||The Methodist Hospital Research Institute|