Ignite Creation Date:
2024-05-05 @ 7:15 PM
Last Modification Date:
2024-10-26 @ 9:46 AM
Study NCT ID:
NCT00632268
Status:
COMPLETED
Last Update Posted:
2013-08-21
First Post:
2008-03-03
Brief Title:
Low-dose RAD001Everolimus Plus Cisplatin-HDFL Chemotherapy for the First-line Treatment of Advanced Gastric Cancer
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Phase II Study of Low-dose RAD001Everolimus Plus Cisplatin and HDFL Weekly 24-Hour Infusion of High-dose 5-Fluorouracil and Leucovorin Chemotherapy for First-line Treatment of Unresectable Recurrent or Metastatic Gastric Cancer
Status:
COMPLETED
Status Verified Date:
2013-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary end-point of this study is to evaluate the objective response rates and the secondary end-points are overall survival progression-free survival and safety profile of low-dose RAD001 everolimus plus cisplatin and HDFL weekly 24-hour infusion of high-dose 5-FU and leucovorin chemotherapy in the first-line treatment for patients with unresectable recurrent or metastatic gastric cancer
Detailed Description:
Non-resectable gastric cancer is an incurable disease with a median survival of 4 months if untreated Systemic chemotherapy confers prolongation of survival and improvement of quality of life Regimens containing cisplatin and 5-fluorouracil 5-FU are widely adopted in the world The overall response rate and median overall survival of the P-HDFL regimen cisplatin and weekly 24-hour infusion of high-dose 5-FU and leucovorin for advanced gastric cancer are 60 45-76 95 CI and 10 months respectively This regimen P-HDFL is very popular in Taiwan because of high objective response rates and low treatment-related toxicities Adding a third active chemotherapeutic agent to cisplatin and 5-FU doublet does not seem to improve efficacy Further most of the patients with recurrent or metastatic gastric cancer are frequently associated with a poor general condition which prohibits intensive chemotherapy Therefore combination of P-HDFL with biologic agentssuch as everolimus etcis an attractive alternative
PI3KAktmTOR pathway is actively participating in cell proliferation and survival of human gastric cancers We have recently demonstrated that RAD001everolimusan mTOR inhibitor although with only modest growth inhibitory effects as a single agent has significant synergistic cytotoxicity with cisplatin and 5-FU in gastric cancer cells The concentration of RAD001 needed for synergism with cisplatin and 5-FU is as low as 05 to 5 nM And as expected RAD001 has significant inhibition of downstream molecules such as 4E-BP1 and S6Kinase in human gastric cancer cells It is therefore reasonable to conduct a phase II study to examine if the combination of a relatively low dose of RAD001 and P-HDFL may improve the outcome of advanced gastric cancer
This is an open-label multi-center phase II trial using low-dose RAD001 10 mg po on D1D8D15 plus P-HDFL chemotherapy cisplatin 35 mgm2 ivd 24 hrs on D1 D8 5-FU 2000 mgm2 and leucovorin 300 mgm2 ivd 24 hrs on D1D8D15 in chemotherapy-naïve patients with unresectable locally advanced recurrent or metastatic gastric cancer The treatment will be repeated every 28 days The primary end-point is objective response rates evaluated by RECIST criteria and the secondary end-points are overall survival progression-free survival and safety profile Approximately 41 patients will be enrolled in order to obtain the 37 evaluable patients required by Simon two-stage minimax design All enrolled patients will be subjected to toxicity evaluations but optionally to the correlative translational study of biomarkers in peripheral blood mononuclear cells Patients with massive malignant ascites will optionally participate the study of biomarkers in neoplastic cells in ascites
PI3KAktmTOR pathway is actively participating in cell proliferation and survival of human gastric cancers We have recently demonstrated that RAD001everolimusan mTOR inhibitor although with only modest growth inhibitory effects as a single agent has significant synergistic cytotoxicity with cisplatin and 5-FU in gastric cancer cells The concentration of RAD001 needed for synergism with cisplatin and 5-FU is as low as 05 to 5 nM And as expected RAD001 has significant inhibition of downstream molecules such as 4E-BP1 and S6Kinase in human gastric cancer cells It is therefore reasonable to conduct a phase II study to examine if the combination of a relatively low dose of RAD001 and P-HDFL may improve the outcome of advanced gastric cancer
This is an open-label multi-center phase II trial using low-dose RAD001 10 mg po on D1D8D15 plus P-HDFL chemotherapy cisplatin 35 mgm2 ivd 24 hrs on D1 D8 5-FU 2000 mgm2 and leucovorin 300 mgm2 ivd 24 hrs on D1D8D15 in chemotherapy-naïve patients with unresectable locally advanced recurrent or metastatic gastric cancer The treatment will be repeated every 28 days The primary end-point is objective response rates evaluated by RECIST criteria and the secondary end-points are overall survival progression-free survival and safety profile Approximately 41 patients will be enrolled in order to obtain the 37 evaluable patients required by Simon two-stage minimax design All enrolled patients will be subjected to toxicity evaluations but optionally to the correlative translational study of biomarkers in peripheral blood mononuclear cells Patients with massive malignant ascites will optionally participate the study of biomarkers in neoplastic cells in ascites
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None