Advanced Solid Tumors, Metastatic Breast Cancer, Metastatic Renal Cell Carcinoma
Conditions
Keywords
Advanced solid tumors, Metastatic renal cell carcinoma (mRCC), ER+/HER2-Metastatic breast cancer (MBC), Dose finding study, mTOR, Pl3K, BEZ235, RAD001, Everolimus, Afinitor®, ER+/HER2- metastatic breast cancer
Brief summary
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
Interventions
DRUGRAD001 + BEZ235
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients age 18 years or older * In the dose finding phase, patients with histologically or cytologically confirmed advanced solid malignancies that are metastatic or unresectable * In the dose expansion phase, the enrollment will be limited to patients with: Patients with metastatic renal cell carcinoma (mRCC) whose disease had progressed despite prior treatment with VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor) therapy (at least one but no more than two lines of VEGFR-TKI therapy) Patients with metastatic breast cancer (MBC) which is ER+/HER2-, whose disease had progressed despite prior treatment with at least one but no more than two lines of chemotherapy and at least one prior line of endocrine therapy in the metastatic setting * WHO performance status of 0-2 * Lab parameters within specifically defined criteria * Patients with measurable disease per RECIST 1.0
Exclusion criteria
* Patients who have previously received mTOR inhibitors or PI3K inhibitors * Patients with CNS metastases unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery plus the disease having been stable for at least 2 months without steroid use for at least 1 month prior to the first dose of RAD001 and BEZ235. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs. * Major surgery within 2 weeks prior to study enrollment * Patient taking anti-cancer drug concomitantly * Received radiation within 4 weeks prior to study enrollment (2 weeks if limited field radiation) * Receive chemotherapy 4 weeks prior to study enrollment * Received live attenuated vaccines within 1 week prior to study enrollment * History of HIV * Any other severe and/or uncontrolled medical condition Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT) | First treatment cycle (28 days) | The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment |
| Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235 | First treatment cycle (28 days) | Frequency of DLTs during the first cycle of treatment |
| Number of participants with adverse events and serious adverse events. | 12 months | Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time versus blood concentration profiles | First treatment cycle ( 28 days) | Analysis of pharmacokinetic parameters in blood samples |
| Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase | 8 weeks | CT or MRI imaging parameters to determine the duration of response according to the RECIST 1.0 criteria |
| 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 | 8 weeks | 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. |
| 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 | 8 weeks | CT or magnetic resonance imaging (MRI) imaging parameters to determine the PFS according to the RECIST 1.0 criteria |
Countries
Belgium, France, Italy, New Zealand, Spain, United Kingdom, United States
Outcome results
None listed