Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 9:48 PM
Ignite Modification Date:
2025-12-24 @ 9:48 PM
NCT ID:
NCT01308632
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.
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 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
* 100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
.100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ.(Level 1).One cycle = 28 days. CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
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 mg/m2 ) and -1 (85 mg/m2).
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 nausea/vomiting 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:
NCT01308632
Study Brief:
Protocol Section:
NCT01308632