Temozolomide Plus Bevacizumab in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status (ATAG)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 2

Conditions

Glioblastoma Multiforme

Primary Brain Tumor

Treatments

Drug: Temozolomide

Drug: Bevacizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02898012

P081213

Details and patient eligibility

About

The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is unestablished. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70.

Full description

Elderly patients aged 65 years and older account for approximately 45% of GBM patients, and this figure is expected to rise concurrently with the aging population of most countries. Unfortunately, few trials have been performed in this setting. In elderly patients with good functional status (KPS >70), radiotherapy (RT) prolongs overall survival (OS) without causing a detriment in quality of life compared with palliative care alone. Recently, it was shown that TMZ could be an alternative to RT. In elderly patients with poor functional status at symptom onset (KPS < 70), RT does not appear to be a satisfactory option in this frail population; however, investigators previously found that TMZ alone was associated with improvements in functional status in 1/3 of cases and appeared to increase survival compared with supportive care alone, especially in methylated MGMT promoter patients.

Bevacizumab (Bev) is an antiangiogenic monoclonal antibody targeting VEGF (vascular endothelial growth factor) that is currently used in recurrent GBM, particularly in combination with alkylating agents. Its effect as first line treatment in combination with TMZ and RT is controversial.

In this study, investigators evaluated the efficacy and safety of the upfront combination of TMZ + Bev as an initial treatment for elderly patients with GBM and impaired functional status (KPS <70).

Enrollment

70 patients

Sex

All

Ages

70+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Supratentorial Glioblastoma diagnosed by biopsy.
Patients aged ≥ 70 years
KPS >30 and < 70
Life expectancy > or = 8 weeks
Patients were enrolled at least 14 days after stereotactic biopsy and 28 days after surgical biopsy.
CT or brain MRI was performed within 4 weeks before treatment to rule out haemorrhage.
Included to health social security system
Medical assessment previous to inclusion
Informed consent form

Exclusion criteria

Previous treatment with Surgical resection, RT or chemotherapy to the tumor.
Hemoglobin level < 9 g%
Absolute neutrophil count < 1500
Platelet count < 100.000
ASAT or ALAT levels more than 3 times the upper limit of normal.
Bilirubin levels more than 2 times the upper limit of normal
Creatinin more than 1.5 times the upper limit of normal
Untreated high blood pressure >150/100 mmHg
Congestive cardiac failure
Proteinuria > 1 gr/24h
INR > 1.5 the upper limit of normal
Recent symptomatic haemorrhage
History of abnormal wound healing
Gastrointestinal fistula
Haemoptysis > grade 2 (NCI-CTC)
Intracranial abscess
Coagulation disorder
Active infection requiring intravenous antibiotics
Vascular disease (including myocardial infarction, unstable angina, cerebrovascular disease, peripheral arterial or aortic disease) in the previous 6 months
Malignancy diagnosed in the previous 5 years (except basocellular skin cancer and in situ cervix cancer)
Allergy to dacarbazine, Bevacizumab, Temozolomide or their excipients, recombinant human monoclonal antibodies, or ovarian cells of Chinese hamsters.