Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer
Metastatic Breast Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.|
- The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]phase IB part
- Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS) [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]phase II part
- The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001 [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]phase Ib part
- number of patients with adverse events as a measure of safety and tolerability [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]phase Ib and phase II
- objective response rate [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]phase Ib and phase II
- Overall survival (OS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]phase Ib and phase II
- check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]phaseIb and phaseII
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
gemcitabine 800mg/m2, D1 and D8 iv. every 3 weeks. cisplatin 30mg/m2, D1 and D8 iv. every 3 weeks. RAD001 5mg QD. po.
Afinitor 5mg qd. po.
Other Names:Drug: Gemcitabine
gemcitabine 800mg/m2 iv. D1 and D8 every 3 weeksDrug: Cisplatin
cisplatin 30mg/m2 iv. D1 and D8 every 3 weeks
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01939418
|Korea, Republic of|
|National cancer center|
|Goyangsi, Gyeonggido, Korea, Republic of, 410-769|
|Principal Investigator:||In Hae Park, Doctor||National Cancer Center, Korea|