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

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ClinicalTrials.gov Identifier: NCT02898012
Recruitment Status : Completed
First Posted : September 13, 2016
Last Update Posted : September 13, 2016
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE July 31, 2016
First Posted Date  ICMJE September 13, 2016
Last Update Posted Date September 13, 2016
Study Start Date  ICMJE October 2010
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
  • 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.
  • 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).
  • 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).
  • 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.
  • 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.
  • Radiological responses [ Time Frame: Neuroimaging evaluation repeated every 2 months until 12 months ]
    Response assessment in neuro-oncology (RANO) criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide Plus Bevacizumab in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status
Official Title  ICMJE Temozolomide Plus Bevacizumab Chemotherapy in Supratentorial Glioblastoma in 70 Years and Older Patients With an Impaired Functional Status (KPS<70)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Primary Brain Tumor
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: Temozolomide and Bevacizumab
Single experimental arm with two drugs : Temozolomide and Bevacizumab
Interventions:
  • Drug: Temozolomide
  • Drug: Bevacizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 7, 2016)
70
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02898012
Other Study ID Numbers  ICMJE P081213
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Roche Pharma AG
Investigators  ICMJE
Principal Investigator: Jean-Yves Delattre, MD-PhD Pôle MSN, Groupe Hospitalier Pitié-Salpêtrière
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP