Ignite Creation Date:
2024-05-05 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00231582
Status:
COMPLETED
Last Update Posted:
2011-02-25
First Post:
2005-10-03
Brief Title:
High-dose Chemotherapy With Autologous Stem Cell Transplantation in Poor Prognosis Germ-cell Tumors TAXIF II
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Sequential High-Dose Chemotherapy Combining Two Mobilization and Cyto-Reductive Treatments Followed by Three High-Dose Chemotherapy Regimens Supported by Autologous Stem Cell Transplantation
Status:
COMPLETED
Status Verified Date:
2007-03
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:
High-dose chemotherapy HD-CT is able to circumvent platinum-resistance of resistantrefractory germ-cell tumors GCTs but expectancy of cure remains low New strategies are needed with new drugs and a sequential approach
Patients with relapsed but not absolutely refractory to Cisplatinum-based chemotherapy poor-prognosis GCTs are scheduled to receive 2 cycles combining epirubicin and paclitaxel followed by 3 consecutive HD-CT supported by stem cell transplantation One course will combine Taxol 360 mgm² thiotepa 720 mgm² followed by two ICE regimens Ifosfamide 12 gm² carboplatin AUC 20 etoposide 1500 mgm²
This phase II study is designed as a Gehan method The main objective of the study is the complete response rate With this aim in view it is planned to enroll in its first step 14 patients to insure that if no complete response CR is noticed study would be stopped for inefficacy ie a CR rate lower than 20 If one or more CR are noticed protocol specified that up to 45 patients will be included in order to reduce the confidence interval CI of the CR rate Secondary objectives are the overall response rate RR the overall survival OS and the progression-free survival PFS rates toxicity and toxic death rate The statistical analysis is done in terms of intent-to-treat
Patients with relapsed but not absolutely refractory to Cisplatinum-based chemotherapy poor-prognosis GCTs are scheduled to receive 2 cycles combining epirubicin and paclitaxel followed by 3 consecutive HD-CT supported by stem cell transplantation One course will combine Taxol 360 mgm² thiotepa 720 mgm² followed by two ICE regimens Ifosfamide 12 gm² carboplatin AUC 20 etoposide 1500 mgm²
This phase II study is designed as a Gehan method The main objective of the study is the complete response rate With this aim in view it is planned to enroll in its first step 14 patients to insure that if no complete response CR is noticed study would be stopped for inefficacy ie a CR rate lower than 20 If one or more CR are noticed protocol specified that up to 45 patients will be included in order to reduce the confidence interval CI of the CR rate Secondary objectives are the overall response rate RR the overall survival OS and the progression-free survival PFS rates toxicity and toxic death rate The statistical analysis is done in terms of intent-to-treat
Detailed Description:
The treatment is designed for relapsed poor prognosis patients with testicular or extra-gonadal GCTs previously treated with cisplatin-containing regimens
Poor prognosis patients are defined as either relapsedrefractory patients more than one month after cisplatin administration whether in the course of first-line CT or in that of salvage treatment or patients who showed evidence of progression after at least 2 lines of cisplatin-containing CT ie BEP and VeIP
Eligibility requirements includes the following criteria age 18 years and 65 performance status 3 histologically or biologically documented GCTs testicular abdominal or mediastinal tumors measurable or evaluable disease life expectancy 3 months normal cardiac liver and renal function tests absence of infection HIV negative test and signed informed consent All patients had to have been previously treated with at least one line of a cisplatin-containing regimen and were included if they were refractory after one or two lines of cisplatin-based CT or had relapsed after two lines of a cisplatin-based CT
Non-inclusion criteria are patients with BEYER score 3 growing teratoma syndrome possibility of being treated with a conventional cisplatin-based CT and previous HD-CT regimen
During the initial evaluation each patient must have a clinical evaluation that includes measurements of tumor marker levels and an imaging work up The tumor marker levels are determined every week during all the sequence of treatment normal level 10 ngml for alpha-foetoprotein and 2 mUmL for HCG The tumor mass is measured after the first two cycles of inductionmobilization therapy and at the end of the treatment
Chemotherapy patients are scheduled to receive 2 courses of front-line mobilization CT followed by 3 HD-CT supported by PBSCT The front-line treatment consists in a combination of epirubicin 100 mgm² in a 30-minute infusion and paclitaxel Taxol 250 mgm² given in a 3-hour infusion administered both on days 1 and 14 These 2 cycles are supported by filgrastim Neupogen 5 µgkg twice a day from days 2 and 15 respectively until apheresis performed on days 10-13 and 24-27 Apheresis is stopped when at least 9 x 106 CD34 cellsKg of BW are obtained for the 3 grafts A third cycle is permitted if the number of CD34 cells is not achieved after the first 2 cycles provided the patient was responsive to CT or for any reason decided upon by the investigator
The first HD-CT regimen consists in an association of thiotepa 720 mgm² and taxol 360 mgm² both administered in a continuous infusion over 3 days D34 to D36 The first pack of CD34 cells is infused on day 39 The second and the third courses ICE scheduled on days 62-66 and 90-94 respectively consist in a combination of etoposide 150 mgm² twice a day in a 2-hour infusion for 5 days ifosfamide 2 400 mgm²d in a 3-hour infusion for 5 days supported by sodium mercaptoethanesulfonate mesna in a 30-minute infusion every 3 hours during a 12-hour period initiated at the same time as the ifosfamide infusion and carboplatin AUC 4d in a 6-hour infusion for 5 days Infusion of PBSCs is planned on days 71 and 99 During the 3 high-dose therapies G-CSF is administered at a daily dose of 5µgkg from the day of PBSC infusion until PMN recovery ie PMN 15 x 109L Each of these ICE regimens is delayed if the PMN level is less than 15 x 109L andor the platelet level less than 100 x 109L
Toxicity and response to therapy are evaluated according to the ECOG and WHO criteria The duration of response is calculated from the date of documented response to the date of progression The duration of PFS and OS are calculated from the date of inclusion to the date of progression or death if no progression PFS and the date of death OS according to Kaplan-Meiers method Survival curves are established according to the classification proposed by BEYER et al Progression death from treatment and withdrawal from protocol for whatever reason are considered as treatment failures Whenever possible patients in clinical partial response PR with normal tumor markers PRm- will be proposed for surgery of residual masses at the end of the whole procedure Sequential procedures are proposed in the case of multiple metastatic sites If surgery is complete and the pathological examination does not show any viable tumor patients will be considered as complete responders If surgery is complete and the pathological examination showed persistent viable tumor they will be considered as surgical complete response
Poor prognosis patients are defined as either relapsedrefractory patients more than one month after cisplatin administration whether in the course of first-line CT or in that of salvage treatment or patients who showed evidence of progression after at least 2 lines of cisplatin-containing CT ie BEP and VeIP
Eligibility requirements includes the following criteria age 18 years and 65 performance status 3 histologically or biologically documented GCTs testicular abdominal or mediastinal tumors measurable or evaluable disease life expectancy 3 months normal cardiac liver and renal function tests absence of infection HIV negative test and signed informed consent All patients had to have been previously treated with at least one line of a cisplatin-containing regimen and were included if they were refractory after one or two lines of cisplatin-based CT or had relapsed after two lines of a cisplatin-based CT
Non-inclusion criteria are patients with BEYER score 3 growing teratoma syndrome possibility of being treated with a conventional cisplatin-based CT and previous HD-CT regimen
During the initial evaluation each patient must have a clinical evaluation that includes measurements of tumor marker levels and an imaging work up The tumor marker levels are determined every week during all the sequence of treatment normal level 10 ngml for alpha-foetoprotein and 2 mUmL for HCG The tumor mass is measured after the first two cycles of inductionmobilization therapy and at the end of the treatment
Chemotherapy patients are scheduled to receive 2 courses of front-line mobilization CT followed by 3 HD-CT supported by PBSCT The front-line treatment consists in a combination of epirubicin 100 mgm² in a 30-minute infusion and paclitaxel Taxol 250 mgm² given in a 3-hour infusion administered both on days 1 and 14 These 2 cycles are supported by filgrastim Neupogen 5 µgkg twice a day from days 2 and 15 respectively until apheresis performed on days 10-13 and 24-27 Apheresis is stopped when at least 9 x 106 CD34 cellsKg of BW are obtained for the 3 grafts A third cycle is permitted if the number of CD34 cells is not achieved after the first 2 cycles provided the patient was responsive to CT or for any reason decided upon by the investigator
The first HD-CT regimen consists in an association of thiotepa 720 mgm² and taxol 360 mgm² both administered in a continuous infusion over 3 days D34 to D36 The first pack of CD34 cells is infused on day 39 The second and the third courses ICE scheduled on days 62-66 and 90-94 respectively consist in a combination of etoposide 150 mgm² twice a day in a 2-hour infusion for 5 days ifosfamide 2 400 mgm²d in a 3-hour infusion for 5 days supported by sodium mercaptoethanesulfonate mesna in a 30-minute infusion every 3 hours during a 12-hour period initiated at the same time as the ifosfamide infusion and carboplatin AUC 4d in a 6-hour infusion for 5 days Infusion of PBSCs is planned on days 71 and 99 During the 3 high-dose therapies G-CSF is administered at a daily dose of 5µgkg from the day of PBSC infusion until PMN recovery ie PMN 15 x 109L Each of these ICE regimens is delayed if the PMN level is less than 15 x 109L andor the platelet level less than 100 x 109L
Toxicity and response to therapy are evaluated according to the ECOG and WHO criteria The duration of response is calculated from the date of documented response to the date of progression The duration of PFS and OS are calculated from the date of inclusion to the date of progression or death if no progression PFS and the date of death OS according to Kaplan-Meiers method Survival curves are established according to the classification proposed by BEYER et al Progression death from treatment and withdrawal from protocol for whatever reason are considered as treatment failures Whenever possible patients in clinical partial response PR with normal tumor markers PRm- will be proposed for surgery of residual masses at the end of the whole procedure Sequential procedures are proposed in the case of multiple metastatic sites If surgery is complete and the pathological examination does not show any viable tumor patients will be considered as complete responders If surgery is complete and the pathological examination showed persistent viable tumor they will be considered as surgical complete response
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