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

Primary Purpose

Glioblastoma Multiforme, Primary Brain Tumor

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Temozolomide

Bevacizumab

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma Multiforme, temozolomide, bevacizumab

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept 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.

Sites / Locations

Groupe Hospitalier Pitié-Salpêtrière

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide and Bevacizumab

Arm Description

Single experimental arm with two drugs : Temozolomide and Bevacizumab

Outcomes

Primary Outcome Measures

Median Overall Survival (OS)

OS calculated from the date of surgery until death from any cause or up to 36 months.

Secondary Outcome Measures

Progression-free survival (PFS)

PFS calculated from the date of surgery to the date of progression or death or up to 36 months.

Toxicity grade according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE, version 3.0)

Assessment every 2 weeks until 12 months by physical and neurological examinations, complete blood counts and urine strip tests. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE, version 3.0).

Health-related quality of life using QLQ-C30 questionnaire

The QLQ-C30 questionnaire includes 30 questions comprising five functioning scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, vomiting and pain) and six single item scales (dyspnea, insomnia, constipation, anorexia, diarrhea, and financial difficulties).

Health-related quality of life using QLQ-BN20

The QLQ-BN20 questionnaire includes 20 items covering functional deficits, symptoms, toxic effects of treatment, and uncertainty about the future.

Cognitive assessment MMSEs

The MMSE was used as a measure of general cognitive status. Higher scores on this exam, which uses a 30-point scale, indicate better cognitive function.

Radiological responses

Response assessment in neuro-oncology (RANO) criteria

Full Information

NCT ID

NCT02898012

First Posted

July 31, 2016

Last Updated

September 7, 2016

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Roche Pharma AG

1. Study Identification

Unique Protocol Identification Number

NCT02898012

Brief Title

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

Acronym

ATAG

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

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Roche Pharma AG

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme, Primary Brain Tumor

Keywords

Glioblastoma Multiforme, temozolomide, bevacizumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Temozolomide and Bevacizumab

Arm Type

Experimental

Arm Description

Single experimental arm with two drugs : Temozolomide and Bevacizumab

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Intervention Description

Temozolomide (TMZ) Temozolomide (TMZ) administered at 130-150 mg/m2 for 5 consecutive days every 4 weeks up to 12 cycles. IV or oral administration was allowed according to the clinical status. TMZ starts at 130 mgs/m2 and increase to 150 mgs/m2 during the second cycle in the absence of hematologic toxicity. In the case of grade 3 or 4 toxicity, the dose for the next cycle is decreased to 110 mg/m2. If the grade 3 or 4 toxicity persists at a dose of 110 mg/m2, treatment is discontinued.

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Intervention Description

Bevacizumab (Bev) administered at a dose of 10 mgs/kg every 2 weeks. Bev was interrupted in cases of wound healing disturbances, gastrointestinal perforation, intestinal occlusion, fistula, uncontrolled hypertension, nephrotic syndrome, grade 4 or recurrent grade 3 thromboembolic events, arterial thrombosis, hemorrhage > grade 2, left ventricular failure, or posterior reversible leukoencephalopathy.

Primary Outcome Measure Information:

Title

Median Overall Survival (OS)

Description

OS calculated from the date of surgery until death from any cause or up to 36 months.

Time Frame

OS calculated from the date of surgery until death or up to 36 months.

Secondary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

PFS calculated from the date of surgery to the date of progression or death or up to 36 months.

Time Frame

PFS calculated from the date of surgery until the date of first documented progression or up to 36 months.

Title

Toxicity grade according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE, version 3.0)

Description

Time Frame

Assessment every 2 weeks until 12 months

Title

Health-related quality of life using QLQ-C30 questionnaire

Description

Time Frame

at baseline and every month until 12 months

Title

Health-related quality of life using QLQ-BN20

Description

The QLQ-BN20 questionnaire includes 20 items covering functional deficits, symptoms, toxic effects of treatment, and uncertainty about the future.

Time Frame

at baseline and every month until 12 months

Title

Cognitive assessment MMSEs

Description

The MMSE was used as a measure of general cognitive status. Higher scores on this exam, which uses a 30-point scale, indicate better cognitive function.

Time Frame

at baseline and they were repeated every month until 12 months

Title

Radiological responses

Description

Response assessment in neuro-oncology (RANO) criteria

Time Frame

Neuroimaging evaluation repeated every 2 months until 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean-Yves Delattre, MD-PhD

Organizational Affiliation

Pôle MSN, Groupe Hospitalier Pitié-Salpêtrière

Official's Role

Principal Investigator

Facility Information:

Facility Name

Groupe Hospitalier Pitié-Salpêtrière

City

Paris

ZIP/Postal Code

75013

Country

France

12. IPD Sharing Statement

Plan to Share IPD

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

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