Clinical trial NCT01805453: Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma
Official title: Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma- A Randomized Multicenter Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Newly-diagnosed Glioblastoma
Keywords: Glioblastoma
Angiotensin-II inhibitors
Losartan
steroids
Radiotherapy
Edema
Randomized trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: ANOCEF (french association of neuro-oncologists)
First posted: 2013-03-06
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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"

Primary outcomes:
measure: Steroid dosage required to control brain edema on the last day of radiotherapy in each arm
timeFrame: Up to Day 42+ 1 month
Secondary outcomes:
measure: Steroids dosage 1 month after the end of RT
timeFrame: Day 42+ 1 month
measure: Assessment of cerebral edema on MRI
timeFrame: Day -28 at -13, Day 42, Day 42+1 month
measure: Tolerance (NCI-CTCAE v3.0)
timeFrame: up to day42 +1 month + 7 days
measure: Blood pressure
timeFrame: Day -10 at -7, Day0, 42, Day 42+1month
measure: HbA1C
timeFrame: Day -10 at -7, D42, Day 42+1month
measure: glycemia
timeFrame: Day -10 at -7, Day14, 28, 42, Day 42+1month
measure: body weight
timeFrame: Day -10 at -7, Day42, Day 42+1month
measure: side-effects of steroids
timeFrame: up to day42 +1 month
measure: Executive functions ( " Moca test ")
timeFrame: Day-10 at -7, Day 42, Day 42+1 month
measure: Quality of life (EORTC)
timeFrame: Day-10 at -7, Day 42, Day 42+1 month
measure: Progression free survival
timeFrame: up to 24 months
measure: Overall survival
timeFrame: up to 24 months
measure: Survival
timeFrame: at 1 year, 2 year
measure: Performance status (KPS) at the end, 1 month , and 2 months after the end of RT
timeFrame: at the end, 1 month, and 2 months after the end of RT
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Neurology Department - Avicenne Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Antoine CARPENTIER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.