Ignite Creation Date:
2024-05-05 @ 5:04 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00384878
Status:
UNKNOWN
Last Update Posted:
2009-02-09
First Post:
2006-10-04
Brief Title:
Study of Cetuximab Plus P-HDFL for the First-Line Treatment of Advanced Gastric Cancer
Sponsor:
Far Eastern Memorial Hospital
Organization:
Far Eastern Memorial Hospital
Study Overview
Official Title:
A Phase II Study of Cetuximab Plus P-HDFL Cisplatin and Weekly 24-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin for the First-Line Treatment of Advanced Gastric Cancer
Status:
UNKNOWN
Status Verified Date:
2006-06
Last Known Status:
RECRUITING
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 the study is confirmed objective response rate complete response CR and partial response PR A response rate of 80 percent for cetuximab plus cisplatin and weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin P-HDFL chemotherapy is assumed The Simon two-stage design will be used for P1 - P0 020 The response rates of interest are P0 60 and P1 80 The investigators will reject cetuximab plus P-HDFL chemotherapy if the response rate is 813 at the first stage and will reject the cetuximab plus P-HDFL chemotherapy if the response rate is 2535 at the second stage If there are more than 8 responses in 13 patients in the first stage the study will continue to a total of 35 patients in the second stage If there are more than 25 responses in 35 patients in the second stage this treatment will be acceptable with a p-value of 005 and of 020 Evaluable patients for response will be those who received at least 4 doses of cetuximab ie one cycle of protocol treatment All enrolled patients will be subjected to toxicity evaluations
The primary end point of the study is confirmed objective response rates by RECIST Response Evaluation Criteria in Solid Tumors The secondary end points of the study are progression-free survival overall survival and treatment-related toxicities
The analysis of response to treatment will be restricted to the eligible patients with at least one measurable lesion The safety analysis will be restricted to the patients who received at least one cycle of the administered chemotherapy The time-to-event end points will be estimated using the method of Kaplan and Meier and based on the intent-to-treat principle Overall survival will be defined as the time interval between the date of study entry and the date of death Progression-free survival will be defined as the time interval between the date of study entry and the date of disease progression or death whichever occurred first Duration of response will be defined as the time interval between the date of initial objective response and the date of disease progression which is only for responders If the event is not yet observed at the time of the last record the patient will be censored at that time point
The primary end point of the study is confirmed objective response rates by RECIST Response Evaluation Criteria in Solid Tumors The secondary end points of the study are progression-free survival overall survival and treatment-related toxicities
The analysis of response to treatment will be restricted to the eligible patients with at least one measurable lesion The safety analysis will be restricted to the patients who received at least one cycle of the administered chemotherapy The time-to-event end points will be estimated using the method of Kaplan and Meier and based on the intent-to-treat principle Overall survival will be defined as the time interval between the date of study entry and the date of death Progression-free survival will be defined as the time interval between the date of study entry and the date of disease progression or death whichever occurred first Duration of response will be defined as the time interval between the date of initial objective response and the date of disease progression which is only for responders If the event is not yet observed at the time of the last record the patient will be censored at that time point
Detailed Description:
Non-resectable gastric cancer is an incurable disease 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 A P-HDFL regimen based primarily on weekly 24-hour infusion of cisplatin and high-dose 5-FU and leucovorin is commonly used in Taiwan for patients with advanced gastric cancer the overall response rate is around 60 45-76 95 CI and the patients compliance is excellent
Expression of EGF and EGFR was detected in about 621 and 515 gastric cancer tissues respectively Tumors with simultaneous expression of EGF TGF-alpha EGFR and p185c-erbB-2 were associated with a high BrdU labeling index rapid tumor growth and an unfavorable outcome Teramoto et al have shown a dose-dependent growth inhibition of an anti-EGFR monoclonal antibody MoAb 528 on EGFR-overexpressing human gastric cancer cells both in vitro and in vivo We have recently demonstrated that cetuximab is cytotoxic to human gastric cancer cells and cetuximab has a chemo-sensitizing effect for cisplatin and 5-FU in human gastric cancer cells Yeh et al unpublished observation We hypothesize that the combination of cetuximab with P-HDFL will further improve the efficacy of the latter on advanced gastric cancer
This is a multi-center prospective phase II trial Patients with histologically proven nonresectable or recurrentmetastatic gastric adenocarcinoma with at least one measurable lesion no prior chemotherapy or radiotherapy and adequate baseline organ functions will be eligible Cetuximab Erbitux Merck Germany 400 mgm2 will be given as an intravenous IV infusion initially ie day 1 of cycle 1 and then followed by weekly IV infusions of cetuximab 250 mgm2 ie days 8 15 22 of cycle 1 and days 1 8 15 22 of cycle 2 and subsequent 28-day cycles Cisplatin will be given as a 24-hour continuous IV infusion in a dose of 35 mgm2day admixing with 5-FU 2000 mgm2 and leucovorin folinic acid 300 mgm2 day 1 and day 8 A 24-hour continuous IV infusion of 5-FU 2000 mgm2 and leucovorin 300 mgm2 will be given on day 15 The cycles will be repeated every 28 days and the response evaluation will be performed every two cycles and at the end of protocol treatment Confirmed objective response rate by RECIST Response Evaluation Criteria in Solid Tumors will be the primary end-point Using the Simon two-stage design for phase II study P1 - P0 020 with the response rates of interest being P0 60 and P1 80 a total of 35 patients are planned to be enrolled in an estimated enrollment period of 12 to 18 months
Expression of EGF and EGFR was detected in about 621 and 515 gastric cancer tissues respectively Tumors with simultaneous expression of EGF TGF-alpha EGFR and p185c-erbB-2 were associated with a high BrdU labeling index rapid tumor growth and an unfavorable outcome Teramoto et al have shown a dose-dependent growth inhibition of an anti-EGFR monoclonal antibody MoAb 528 on EGFR-overexpressing human gastric cancer cells both in vitro and in vivo We have recently demonstrated that cetuximab is cytotoxic to human gastric cancer cells and cetuximab has a chemo-sensitizing effect for cisplatin and 5-FU in human gastric cancer cells Yeh et al unpublished observation We hypothesize that the combination of cetuximab with P-HDFL will further improve the efficacy of the latter on advanced gastric cancer
This is a multi-center prospective phase II trial Patients with histologically proven nonresectable or recurrentmetastatic gastric adenocarcinoma with at least one measurable lesion no prior chemotherapy or radiotherapy and adequate baseline organ functions will be eligible Cetuximab Erbitux Merck Germany 400 mgm2 will be given as an intravenous IV infusion initially ie day 1 of cycle 1 and then followed by weekly IV infusions of cetuximab 250 mgm2 ie days 8 15 22 of cycle 1 and days 1 8 15 22 of cycle 2 and subsequent 28-day cycles Cisplatin will be given as a 24-hour continuous IV infusion in a dose of 35 mgm2day admixing with 5-FU 2000 mgm2 and leucovorin folinic acid 300 mgm2 day 1 and day 8 A 24-hour continuous IV infusion of 5-FU 2000 mgm2 and leucovorin 300 mgm2 will be given on day 15 The cycles will be repeated every 28 days and the response evaluation will be performed every two cycles and at the end of protocol treatment Confirmed objective response rate by RECIST Response Evaluation Criteria in Solid Tumors will be the primary end-point Using the Simon two-stage design for phase II study P1 - P0 020 with the response rates of interest being P0 60 and P1 80 a total of 35 patients are planned to be enrolled in an estimated enrollment period of 12 to 18 months
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