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

September 7, 2016 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Groupe Hospitalier Pitie-Salpetriere

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

68 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temozolomide and Bevacizumab
Single experimental arm with two drugs : Temozolomide and Bevacizumab
Drug: Temozolomide
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.
Drug: Bevacizumab
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Overall Survival (OS)
Time Frame: OS calculated from the date of surgery until death or up to 36 months.
OS calculated from the date of surgery until death from any cause or up to 36 months.
OS calculated from the date of surgery until death or up to 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: PFS calculated from the date of surgery until the date of first documented progression or up to 36 months.
PFS calculated from the date of surgery to the date of progression or death or up to 36 months.
PFS calculated from the date of surgery until the date of first documented progression or up to 36 months.
Toxicity grade according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE, version 3.0)
Time Frame: Assessment every 2 weeks until 12 months
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).
Assessment every 2 weeks until 12 months
Health-related quality of life using QLQ-C30 questionnaire
Time Frame: at baseline and every month until 12 months
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).
at baseline and every month until 12 months
Health-related quality of life using QLQ-BN20
Time Frame: at baseline and every month until 12 months
The QLQ-BN20 questionnaire includes 20 items covering functional deficits, symptoms, toxic effects of treatment, and uncertainty about the future.
at baseline and every month until 12 months
Cognitive assessment MMSEs
Time Frame: at baseline and they were repeated every month until 12 months
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.
at baseline and they were repeated every month until 12 months
Radiological responses
Time Frame: Neuroimaging evaluation repeated every 2 months until 12 months
Response assessment in neuro-oncology (RANO) criteria
Neuroimaging evaluation repeated every 2 months until 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Jean-Yves Delattre, MD-PhD, Pôle MSN, Groupe Hospitalier Pitié-Salpêtrière

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

July 31, 2016

First Submitted That Met QC Criteria

September 7, 2016

First Posted (Estimate)

September 13, 2016

Study Record Updates

Last Update Posted (Estimate)

September 13, 2016

Last Update Submitted That Met QC Criteria

September 7, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P081213

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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