Dose Finding Study of RAD001 (Everolimus, Afinitor�) in Combination With BEZ235 in Patients With Advanced Solid Tumors
Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Advanced Solid Tumors; Metastatic Breast Cancer; Metastatic Renal Cell Carcinoma
Intervention: RAD001 + BEZ235 (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Novartis Pharmaceuticals Official(s) and/or principal investigator(s): Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals
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
Clinical Details
Official title: An Open-label, Multi-center Phase I Dose-finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235 Number of participants with adverse events and serious adverse events.
Secondary outcome: Time versus blood concentration profilesOverall 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 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 Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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/exclusion criteria may apply
Locations and Contacts
Novartis Investigative Site, Wilrijk 2610, Belgium
Novartis Investigative Site, Bordeaux Cedex 33075, France
Novartis Investigative Site, Montellier cedex 5 34298, France
Novartis Investigative Site, Auckland, New Zealand
Highlands Oncology Group Dept of Highlands Oncology Grp, Fayetteville, Arkansas 72703, United States
Novartis Investigative Site, Barcelona, Catalunya 08035, Spain
Washington University School of Medicine Washington University (16), St. Louis, Missouri 63110, United States
Novartis Investigative Site, High Heaton, Newcastle Upon Tyne NE7 7DN, United Kingdom
Medical University of South Carolina SC, Charleston, South Carolina 29425, United States
Novartis Investigative Site, Verona, VR 37126, Italy
Additional Information
Starting date: January 2012
Last updated: February 26, 2015
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