Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma (ASTER)
Primary Purpose
Newly-diagnosed Glioblastoma
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Losartan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Newly-diagnosed Glioblastoma focused on measuring Glioblastoma, Angiotensin-II inhibitors, Losartan, steroids, Radiotherapy, Edema, Randomized trial
Eligibility Criteria
Inclusion Criteria:
- 18 years or older
- Histologically confirmed glioblastoma (Grade 4 WHO)
- patients eligible for radiotherapy and concomitant Temozolomide
- KPS ≥ 50%
- Adequate hematologic, liver and renal functions
Exclusion Criteria:
- Patients unable to undergo an MRI with contrast
- Patients without any residual tumor left on the screening MRI of both flair and contrast-enhanced lesions complete surgical resection)
- Any prior treatment of glioblastoma including any local therapy (immunotherapy, Gliadel wafers, …..) during or after surgical resection
- Any on-going treatment for high blood pressure at time of inclusion, whatever the therapeutic class of drugs
- Systolic blood pressure <110 mmHg.
- relative or definite contra-indication to Losartan:
- Pregnant or breast feeding women; Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception
- Non-affiliation to the "sécurité sociale"
Sites / Locations
- Neurology Department - Avicenne Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Arm A: Losartan
Arm B: Placebo
Arm Description
Arm A: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan 50mg*2/day until the halting for any reason
Arm B: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason
Outcomes
Primary Outcome Measures
Steroid dosage required to control brain edema on the last day of radiotherapy in each arm
Secondary Outcome Measures
Steroids dosage 1 month after the end of RT
Assessment of cerebral edema on MRI
Tolerance (NCI-CTCAE v3.0)
To be reported according to NCI/CTC version 3.0 (adverse events)
Blood pressure
HbA1C
glycemia
body weight
side-effects of steroids
Executive functions ( " Moca test ")
Quality of life (EORTC)
Progression free survival
Overall survival
Survival
Performance status (KPS) at the end, 1 month , and 2 months after the end of RT
Full Information
NCT ID
NCT01805453
First Posted
February 25, 2013
Last Updated
May 7, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
ANOCEF (french association of neuro-oncologists)
1. Study Identification
Unique Protocol Identification Number
NCT01805453
Brief Title
Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma
Acronym
ASTER
Official Title
Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma- A Randomized Multicenter Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
March 29, 2013 (Actual)
Primary Completion Date
January 15, 2015 (Actual)
Study Completion Date
May 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
ANOCEF (french association of neuro-oncologists)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To assess the efficacy of an Angiotensin-II inhibitor (Losartan) to reduce peritumoral edema in newly diagnosed glioblastoma patients.
Detailed Description
Multicentre, randomized (1:1), double blinded trial:- Arm A: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan 50mg*2/day until the halting for any reason - Arm B: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Newly-diagnosed Glioblastoma
Keywords
Glioblastoma, Angiotensin-II inhibitors, Losartan, steroids, Radiotherapy, Edema, Randomized trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Losartan
Arm Type
Active Comparator
Arm Description
Arm A: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan 50mg*2/day until the halting for any reason
Arm Title
Arm B: Placebo
Arm Type
Placebo Comparator
Arm Description
Arm B: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason
Intervention Type
Drug
Intervention Name(s)
Losartan
Intervention Description
Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan or placebo (Arm A or B) 50mg*2/day until the halting for any reason
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason
Primary Outcome Measure Information:
Title
Steroid dosage required to control brain edema on the last day of radiotherapy in each arm
Time Frame
Up to Day 42+ 1 month
Secondary Outcome Measure Information:
Title
Steroids dosage 1 month after the end of RT
Time Frame
Day 42+ 1 month
Title
Assessment of cerebral edema on MRI
Time Frame
Day -28 at -13, Day 42, Day 42+1 month
Title
Tolerance (NCI-CTCAE v3.0)
Description
To be reported according to NCI/CTC version 3.0 (adverse events)
Time Frame
up to day42 +1 month + 7 days
Title
Blood pressure
Time Frame
Day -10 at -7, Day0, 42, Day 42+1month
Title
HbA1C
Time Frame
Day -10 at -7, D42, Day 42+1month
Title
glycemia
Time Frame
Day -10 at -7, Day14, 28, 42, Day 42+1month
Title
body weight
Time Frame
Day -10 at -7, Day42, Day 42+1month
Title
side-effects of steroids
Time Frame
up to day42 +1 month
Title
Executive functions ( " Moca test ")
Time Frame
Day-10 at -7, Day 42, Day 42+1 month
Title
Quality of life (EORTC)
Time Frame
Day-10 at -7, Day 42, Day 42+1 month
Title
Progression free survival
Time Frame
up to 24 months
Title
Overall survival
Time Frame
up to 24 months
Title
Survival
Time Frame
at 1 year, 2 year
Title
Performance status (KPS) at the end, 1 month , and 2 months after the end of RT
Time Frame
at the end, 1 month, and 2 months after the end of RT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years or older
Histologically confirmed glioblastoma (Grade 4 WHO)
patients eligible for radiotherapy and concomitant Temozolomide
KPS ≥ 50%
Adequate hematologic, liver and renal functions
Exclusion Criteria:
Patients unable to undergo an MRI with contrast
Patients without any residual tumor left on the screening MRI of both flair and contrast-enhanced lesions complete surgical resection)
Any prior treatment of glioblastoma including any local therapy (immunotherapy, Gliadel wafers, …..) during or after surgical resection
Any on-going treatment for high blood pressure at time of inclusion, whatever the therapeutic class of drugs
Systolic blood pressure <110 mmHg.
relative or definite contra-indication to Losartan:
Pregnant or breast feeding women; Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception
Non-affiliation to the "sécurité sociale"
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoine CARPENTIER, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurology Department - Avicenne Hospital
City
Bobigny
ZIP/Postal Code
93000
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
30716716
Citation
Ursu R, Thomas L, Psimaras D, Chinot O, Le Rhun E, Ricard D, Charissoux M, Cuzzubbo S, Sejalon F, Quillien V, Hoang-Xuan K, Ducray F, Portal JJ, Tibi A, Mandonnet E, Levy-Piedbois C, Vicaut E, Carpentier AF. Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study. Eur J Cancer. 2019 Mar;109:129-136. doi: 10.1016/j.ejca.2018.12.025. Epub 2019 Feb 1.
Results Reference
derived
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Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma
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