Study has two parts: 1. Dose-finding: to determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of RAD001 (everolimus , Afinitor®) in combination with BEZ235 in patients with advanced solid tumors. 2. Dose-expansion: to assess safety and tolerability of RAD001 and BEZ235 at the MTD in patients with ER+/HER2- metastatic breast cancer and metastatic renal cell cancer
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
RAD001 is formulated as tablets of 2.5 mg and 5 mg strength, blistered in units of 10 tablets (for oral use) each. Blisters should be opened only at the time of dministration as the drug is both hygroscopic and light-sensitive. RAD001 should be administered immediately after a meal with a large glass of water. BEZ235 is supplied as 50-mg, 200-mg, 300-mg and 400-mg sachets (for oral use). BEZ235 is packaged in aluminum foil bags. Bags are packaged in a box. Patients will receive RAD001 in combination with BEZ235.
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States
Washington University School of Medicine Washington University (16)
St Louis, Missouri, United States
Medical University of South Carolina SC
Charleston, South Carolina, United States
Novartis Investigative Site
Wilrijk, Belgium
Novartis Investigative Site
Bordeaux, France
Novartis Investigative Site
Montellier Cedex 5, France
Novartis Investigative Site
Verona, VR, Italy
Novartis Investigative Site
Auckland, New Zealand
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
High Heaton, Newcastle Upon Tyne, United Kingdom
Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment
Time frame: First treatment cycle (28 days)
Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235
Frequency of DLTs during the first cycle of treatment
Time frame: First treatment cycle (28 days)
Number of participants with adverse events and serious adverse events.
Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters.
Time frame: 12 months
Time versus blood concentration profiles
Analysis of pharmacokinetic parameters in blood samples
Time frame: First treatment cycle ( 28 days)
Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
CT or MRI imaging parameters to determine the overall response rate (complete response, partial response, stable disease, or progressive disease) according to the RECIST 1.0 criteria.
Time frame: 8 weeks
Progresive Free Survival (PFS) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
CT or magnetic resonance imaging (MRI) imaging parameters to determine the PFS according to the RECIST 1.0 criteria
Time frame: 8 weeks
Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase
CT or MRI imaging parameters to determine the duration of response according to the RECIST 1.0 criteria
Time frame: 8 weeks
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