Clinical trial NCT02898012: Temozolomide Plus Bevacizumab in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status
Official title: Temozolomide Plus Bevacizumab Chemotherapy in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status (KPS<70)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Primary Brain Tumor
Keywords: Glioblastoma Multiforme
temozolomide
bevacizumab
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2016-09-13
Enrollment: 70
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Median Overall Survival (OS)
timeFrame: OS calculated from the date of surgery until death or up to 36 months.
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: PFS calculated from the date of surgery until the date of first documented progression or up to 36 months.
measure: Toxicity grade according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE, version 3.0)
timeFrame: Assessment every 2 weeks until 12 months
measure: Health-related quality of life using QLQ-C30 questionnaire
timeFrame: at baseline and every month until 12 months
measure: Health-related quality of life using QLQ-BN20
timeFrame: at baseline and every month until 12 months
measure: Cognitive assessment MMSEs
timeFrame: at baseline and they were repeated every month until 12 months
measure: Radiological responses
timeFrame: Neuroimaging evaluation repeated every 2 months until 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière
Study officials:
affiliation: Pôle MSN, Groupe Hospitalier Pitié-Salpêtrière
name: Jean-Yves Delattre, MD-PhD
role: PRINCIPAL_INVESTIGATOR
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