BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)
This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Older kidney cancer medications (such as temsirolimus [Torisel®] or everolimus [Afinitor®]) typically only block one mechanism in cancer cells, so the investigators think that BEZ235 may work even better against kidney cancer.
The purpose of the first part of this study is to test the safety of giving BEZ235 at different doses. The investigators are trying to find a safe dose of BEZ235 and want to find out what effects, good and/or bad, it has on the patient and the cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1b/2 Study of BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)|
- maximally tolerated dose (MTD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]The trial follows a standard 3+3 design; a minimum of 4 and maximally 18 patients will be enrolled in cohorts of 3 on 3 different dosing levels. The MTD will be the RP2 dose; determination requires at least 8 patients. Patients will be replaced in case of withdrawal of consent or progressive disease during the DLT evaluation period.
- 4-month PFS rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]for subjects with advanced clear cell RCC and disease progression following prior first-line or second-line therapy with a rapalogue-type mTOR inhibitor (mTORC1 inhibitor), who are treated with BEZ235. PFS will be defined as the duration of time from enrollment until death or progression of disease. Patients still progression free at the time of analysis will be considered censored.
- tolerability and safety profile of BEZ235 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]safety will be characterized in terms of the incidence, timing, severity, and relatedness of adverse events and laboratory abnormalities. Physical examination, vital signs, and ECOG performance status will be serially monitored. Severity will be graded according to the NCI CTCAE Version 4.0.
- objective response rate (ORR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]in patients with advanced clear cell RCC, progressing after prior first-line or second-line mTOR therapy. The determination of antitumor efficacy will be based on objective tumor assessments made according to the RECIST1.1.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||October 2013|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
This is a single-institution, open label, single-arm Phase 1b/2 trial of BEZ235 in patients with advanced RCC. The study will be conducted in two phases:
Phase 1b: dose-escalation will be performed to determine the maximally tolerated dose (MTD) of twice daily BEZ235 to use in Phase 2 (RP2 dose).
Phase 2: subjects with clear cell who have experienced disease progression on prior first or second-line mTOR targeted therapy will be treated on the MTD of twice daily BEZ235.
BEZ235 will be taken orally twice daily starting on Day 1, Cycle 1, self-administration will continue twice daily on a continuous schedule with cycle length defined as 28 days. Increasing dosing levels of BEZ235 will be studied sequentially (beginning with Dose Level 1, BEZ235 400mg by mouth twice daily) as per the treatment noted below.
Cohort-1a BEZ235 300 mg by mouth twice daily Cohort 1 BEZ235 400 mg by mouth twice daily Cohort 2 BEZ235 600 mg by mouth twice daily Cohort 3 BEZ235 800 mg by mouth twice daily
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Ana Molina, MD||Memorial Sloan-Kettering Cancer Center|