Ignite Creation Date:
2024-05-05 @ 11:19 PM
Last Modification Date:
2024-10-26 @ 10:32 AM
Study NCT ID:
NCT01308632
Status:
UNKNOWN
Last Update Posted:
2011-03-04
First Post:
2011-01-24
Brief Title:
Metronomic Temozolamide in Patients With Recurrent Glioblastoma
Sponsor:
Grupo Español de Investigación en Neurooncología
Organization:
Grupo Español de Investigación en Neurooncología
Study Overview
Official Title:
PHASE I-II TRIAL OF METRONOMIC TEMOZOLAMIDE WITH INTERMITTENT INTENSIFICATION AND IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Status:
UNKNOWN
Status Verified Date:
2011-03
Last Known Status:
ACTIVE_NOT_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:
Indication
Subjects with glioblastoma at first relapse after surgery radiotherapy and first-line temozolomide TMZ
Objectives
1 Phase I endpoint
- To determine the maximum tolerated dose MTD of CPT-11 administered on days 8 and 22 in combination with a fixed continuous and metronomic regimen of TMZ given in 28-day cycles
2 Phase II endpoints
Primary endpoint Progression-free survival at 6 months Secondary endpoints Response rate toxicity profile overall survival
Complementary studies
To assess the effect of treatment on plasma concentration of thrombospondin-1 TSP1 soluble VEGF receptor 1 sVEGF-1 and VEGF-A and their correlation with clinical outcome
To assess the correlation between immunohistochemical expression of PTEN and MGMT proteins and clinical outcomes
Subjects with glioblastoma at first relapse after surgery radiotherapy and first-line temozolomide TMZ
Objectives
1 Phase I endpoint
- To determine the maximum tolerated dose MTD of CPT-11 administered on days 8 and 22 in combination with a fixed continuous and metronomic regimen of TMZ given in 28-day cycles
2 Phase II endpoints
Primary endpoint Progression-free survival at 6 months Secondary endpoints Response rate toxicity profile overall survival
Complementary studies
To assess the effect of treatment on plasma concentration of thrombospondin-1 TSP1 soluble VEGF receptor 1 sVEGF-1 and VEGF-A and their correlation with clinical outcome
To assess the correlation between immunohistochemical expression of PTEN and MGMT proteins and clinical outcomes
Detailed Description:
Study Design Open label phase I - II trial Phase I trial TMZ will be administered in a fixed schedule as follows
TMZ
50 mgm2day divided in three daily doses approx 17 mgm28 hours on days 1-7 9-21 and 23-28
100 mgm2 in a morning single dose on days 8 and 22
CPT-11 starting dose
100 mgm2 on days 8 and 22 administered 3 to 6 hours after TMZLevel 1One cycle 28 days CPT-11 will be escalated in successive cohorts of 3 patients as follows 115 130 145 160 mgm2
Three patients will be treated at dose level 1 If there is no DLT 3 new patients will be treated at dose level 2 and so on If 1 or 2 of the 3 patients initially recruited at each treatment level experience DLT 3 additional patients will be included at the same level If DLT is registered in less than 3 of the 6 patients treated at this level 3 new patients will be included in the next dose level If 3 or more of the 6 patients experience DLT the phase I trial will be closed and the previous treatment level will be chosen for the phase II trial If all 3 initial patients at one level experience DLT the previous dose level will be used in the phase II trial
If DLT is found at dose level 1 phase I trial will be re-started at level -2 70 mgm2 and -1 85 mgm2
Definition of DLT
Absolute neutrophil count ANC 500 μl 7 days
Platelet count 25000 μl
A delay in starting a new cycle by 7 days to allow recovery from toxicity ANC 1500 μl and platelet count 100000 μl
Febrile Neutropenia
Non-haematological toxicity grade 3-4 except alopecia and nauseavomiting or diarrhea without adequate prophylaxis or treatment
Phase II trial Patients will receive the treatment schedule at the dose level stated in the phase I study Treatment will be maintained until progression or excessive toxicity
Patient evaluation A physical examination blood count and basic biochemistry assessment will be performed within 3 weeks before treatment and at each study visit Tumor recurrence or progression has to be demonstrated by MRI scan performed within 3 weeks before the first treatment course and after every second course of chemotherapy The assessment of tumor response will be based on criteria defined by Macdonald et al Study visits will be performed on days 1 8 15 and 22 of first and second treatment course and on days 8 and 22 thereafter if no significant toxicity has been observed
Complementary studies The immunohistochemical expression of PTEN and MGMT will be assessed in paraffin sections of tumor tissue of all patients
Blood samples for enzyme immunoassay of TSP1 sVEGFR-1 and VEGF-A will be collected within 3 weeks before treatment after course 1 and every 3 treatment courses thereafter
TMZ
50 mgm2day divided in three daily doses approx 17 mgm28 hours on days 1-7 9-21 and 23-28
100 mgm2 in a morning single dose on days 8 and 22
CPT-11 starting dose
100 mgm2 on days 8 and 22 administered 3 to 6 hours after TMZLevel 1One cycle 28 days CPT-11 will be escalated in successive cohorts of 3 patients as follows 115 130 145 160 mgm2
Three patients will be treated at dose level 1 If there is no DLT 3 new patients will be treated at dose level 2 and so on If 1 or 2 of the 3 patients initially recruited at each treatment level experience DLT 3 additional patients will be included at the same level If DLT is registered in less than 3 of the 6 patients treated at this level 3 new patients will be included in the next dose level If 3 or more of the 6 patients experience DLT the phase I trial will be closed and the previous treatment level will be chosen for the phase II trial If all 3 initial patients at one level experience DLT the previous dose level will be used in the phase II trial
If DLT is found at dose level 1 phase I trial will be re-started at level -2 70 mgm2 and -1 85 mgm2
Definition of DLT
Absolute neutrophil count ANC 500 μl 7 days
Platelet count 25000 μl
A delay in starting a new cycle by 7 days to allow recovery from toxicity ANC 1500 μl and platelet count 100000 μl
Febrile Neutropenia
Non-haematological toxicity grade 3-4 except alopecia and nauseavomiting or diarrhea without adequate prophylaxis or treatment
Phase II trial Patients will receive the treatment schedule at the dose level stated in the phase I study Treatment will be maintained until progression or excessive toxicity
Patient evaluation A physical examination blood count and basic biochemistry assessment will be performed within 3 weeks before treatment and at each study visit Tumor recurrence or progression has to be demonstrated by MRI scan performed within 3 weeks before the first treatment course and after every second course of chemotherapy The assessment of tumor response will be based on criteria defined by Macdonald et al Study visits will be performed on days 1 8 15 and 22 of first and second treatment course and on days 8 and 22 thereafter if no significant toxicity has been observed
Complementary studies The immunohistochemical expression of PTEN and MGMT will be assessed in paraffin sections of tumor tissue of all patients
Blood samples for enzyme immunoassay of TSP1 sVEGFR-1 and VEGF-A will be collected within 3 weeks before treatment after course 1 and every 3 treatment courses thereafter
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