Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00128700
Status:
COMPLETED
Last Update Posted:
2012-09-24
First Post:
2005-08-08
Brief Title:
Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
Phase III Study on Concomitant and Adjuvant Temozolomide and Radiotherapy With or Without PTK787ZK222584 in Newly Diagnosed GBM
Status:
COMPLETED
Status Verified Date:
2012-09
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:
RATIONALE Drugs used in chemotherapy such as temozolomide work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Radiation therapy uses high-energy x-rays to kill tumor cells Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor Giving temozolomide and radiation therapy together with vatalanib may kill more tumor cells
PURPOSE This randomized phase III trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme
PURPOSE This randomized phase III trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme
Detailed Description:
OBJECTIVES
Primary
Determine the maximum tolerated dose and recommended phase II dose of vatalanib when given in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme Phase I
Determine the safety and tolerability of this regimen in these patients Phase I
Determine the 6-month progression-free survival of patients treated with chemoradiotherapy comprising temozolomide and radiotherapy with or without vatalanib followed by adjuvant therapy comprising temozolomide and vatalanib or temozolomide alone with or without maintenance therapy comprising vatalanib alone Phase II
Secondary
Determine 12-month overall survival of patients treated with these regimens Phase II
Determine the toxicity profile of these regimens in these patients Phase II
Correlate expression of angiogenesis and hypoxia markers and MGMT methylation status with clinical outcome in patients treated with these regimens
OUTLINE This is a phase I multicenter open-label non-randomized dose-escalation study of vatalanib followed by a phase II randomized controlled study Patients enrolled in the phase II portion of the study are stratified according to participating center age 50 years vs 50 years corticosteroid intake yes vs no and mini-mental status evaluation score 27 vs 27-29 vs 30
Phase I
Chemoradiotherapy Patients receive oral temozolomide once daily for 6-7 weeks and oral vatalanib once daily for 6 weeks Patients also undergo radiotherapy once daily 5 days a week for 6 weeks Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients continue to receive oral vatalanib twice daily
Cohorts of 3-6 patients receive escalating doses of vatalanib during chemoradiotherapy until the maximum tolerated dose is determined MTD The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity At least 6 patients are treated at the MTD
Adjuvant therapy Patients receive oral temozolomide once daily on days 1-5 and oral vatalanib twice daily on days 1-28 Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive oral vatalanib twice daily in the absence of disease progression or unacceptable toxicity
Phase II Patients are randomized to 1 of 3 treatment arms
Arm I
Chemoradiotherapy Patients receive oral temozolomide once daily for 6-7 weeks and undergo radiotherapy once daily 5 days a week for 6 weeks Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy
Adjuvant therapy Patients receive oral temozolomide once daily on days 1-5 Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity
Arm II
Chemoradiotherapy Patients receive temozolomide and undergo radiotherapy as in arm I Patients also receive vatalanib twice daily for 6 weeks at the MTD determined in phase I Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients continue to receive oral vatalanib twice daily
Adjuvant therapy Patients receive temozolomide and vatalanib as in phase I adjuvant therapy Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive vatalanib as in phase I maintenance therapy
Arm III
Chemoradiotherapy Patients receive temozolomide and undergo radiotherapy as in arm I Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients receive oral vatalanib twice daily
Adjuvant therapy Patients receive temozolomide and vatalanib as in phase I adjuvant therapy Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive vatalanib as in phase I maintenance therapy
After completion of study treatment patients are followed every 3 months for survival
PROJECTED ACCRUAL Approximately 3-18 patients will be accrued for the phase I portion of this study A total of 201 patients 67 per treatment arm will be accrued for the phase II portion of this study
Primary
Determine the maximum tolerated dose and recommended phase II dose of vatalanib when given in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme Phase I
Determine the safety and tolerability of this regimen in these patients Phase I
Determine the 6-month progression-free survival of patients treated with chemoradiotherapy comprising temozolomide and radiotherapy with or without vatalanib followed by adjuvant therapy comprising temozolomide and vatalanib or temozolomide alone with or without maintenance therapy comprising vatalanib alone Phase II
Secondary
Determine 12-month overall survival of patients treated with these regimens Phase II
Determine the toxicity profile of these regimens in these patients Phase II
Correlate expression of angiogenesis and hypoxia markers and MGMT methylation status with clinical outcome in patients treated with these regimens
OUTLINE This is a phase I multicenter open-label non-randomized dose-escalation study of vatalanib followed by a phase II randomized controlled study Patients enrolled in the phase II portion of the study are stratified according to participating center age 50 years vs 50 years corticosteroid intake yes vs no and mini-mental status evaluation score 27 vs 27-29 vs 30
Phase I
Chemoradiotherapy Patients receive oral temozolomide once daily for 6-7 weeks and oral vatalanib once daily for 6 weeks Patients also undergo radiotherapy once daily 5 days a week for 6 weeks Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients continue to receive oral vatalanib twice daily
Cohorts of 3-6 patients receive escalating doses of vatalanib during chemoradiotherapy until the maximum tolerated dose is determined MTD The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity At least 6 patients are treated at the MTD
Adjuvant therapy Patients receive oral temozolomide once daily on days 1-5 and oral vatalanib twice daily on days 1-28 Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive oral vatalanib twice daily in the absence of disease progression or unacceptable toxicity
Phase II Patients are randomized to 1 of 3 treatment arms
Arm I
Chemoradiotherapy Patients receive oral temozolomide once daily for 6-7 weeks and undergo radiotherapy once daily 5 days a week for 6 weeks Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy
Adjuvant therapy Patients receive oral temozolomide once daily on days 1-5 Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity
Arm II
Chemoradiotherapy Patients receive temozolomide and undergo radiotherapy as in arm I Patients also receive vatalanib twice daily for 6 weeks at the MTD determined in phase I Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients continue to receive oral vatalanib twice daily
Adjuvant therapy Patients receive temozolomide and vatalanib as in phase I adjuvant therapy Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive vatalanib as in phase I maintenance therapy
Arm III
Chemoradiotherapy Patients receive temozolomide and undergo radiotherapy as in arm I Four weeks after the completion of chemoradiotherapy patients proceed to adjuvant therapy During the 4-week period between chemoradiotherapy and adjuvant therapy patients receive oral vatalanib twice daily
Adjuvant therapy Patients receive temozolomide and vatalanib as in phase I adjuvant therapy Patients then proceed to maintenance therapy
Maintenance therapy Patients continue to receive vatalanib as in phase I maintenance therapy
After completion of study treatment patients are followed every 3 months for survival
PROJECTED ACCRUAL Approximately 3-18 patients will be accrued for the phase I portion of this study A total of 201 patients 67 per treatment arm will be accrued for the phase II portion of this study
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EORTC-26041 | None | None | None |
| EORTC-22041 | None | None | None |
| EUDRACT-2004-003896-35 | None | None | None |