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Glioblastoma MultiformePhase 2ATAGNCT02898012

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

A Phase 2 study testing Temozolomide and Bevacizumab in people with Glioblastoma Multiforme and Primary Brain Tumor, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Glioblastoma Multiforme, Primary Brain Tumor
What is being tested?
Temozolomide and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteFrance
Study dates
Oct 2010to Jun 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • Included to health social security system
  • Medical assessment previous to inclusion
  • Informed consent form

Who cannot join

  • 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
Show all 21Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Groupe Hospitalier Pitié-Salpêtrière

    Paris, Paris, 75013

Other trials in France

About this study

Official title: 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.

Read the 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).

Keywords
Glioblastoma Multiforme, temozolomide, bevacizumab
Medical subject headings
Glioblastoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemozolomideDrug

    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.

  • BevacizumabDrug

    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 groups in NCT02898012
Study groupRoleWhat they receive
Temozolomide and BevacizumabExperimentalSingle experimental arm with two drugs : Temozolomide and Bevacizumab
Receives: Drug: Temozolomide; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Overall Survival (OS)

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

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

Secondary outcomes (6)

  1. Progression-free survival (PFS)

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

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

  2. 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).

    Measured: Assessment every 2 weeks until 12 months

  3. 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).

    Measured: at baseline and every month until 12 months

  4. 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.

    Measured: at baseline and every month until 12 months

  5. 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.

    Measured: at baseline and they were repeated every month until 12 months

  6. Radiological responses

    Response assessment in neuro-oncology (RANO) criteria

    Measured: Neuroimaging evaluation repeated every 2 months until 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2016 (estimated)
  2. Study startOct 2010
  3. Primary completionMay 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02898012
Sponsor's protocol ID
P081213
Acronym
ATAG
Status last verified
Jul 2016
First submitted
31 Jul 2016
Last updated
13 Sep 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol. 2012 Nov;14 Suppl 5(Suppl 5):v1-49. doi: 10.1093/neuonc/nos218. No abstract available.

    PubMed 23095881

  • Fleury A, Menegoz F, Grosclaude P, Daures JP, Henry-Amar M, Raverdy N, Schaffer P, Poisson M, Delattre JY. Descriptive epidemiology of cerebral gliomas in France. Cancer. 1997 Mar 15;79(6):1195-202. doi: 10.1002/(sici)1097-0142(19970315)79:63.0.co;2-v.

    PubMed 9070498

  • Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Menei P, Loiseau H, Bernier V, Honnorat J, Barrie M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY; Association of French-Speaking Neuro-Oncologists. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35. doi: 10.1056/NEJMoa065901.

    PubMed 17429084

  • Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R; Nordic Clinical Brain Tumour Study Group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012 Sep;13(9):916-26. doi: 10.1016/S1470-2045(12)70265-6. Epub 2012 Aug 8.

    PubMed 22877848

  • Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. doi: 10.1016/S1470-2045(12)70164-X. Epub 2012 May 10.

    PubMed 22578793

  • Gallego Perez-Larraya J, Ducray F, Chinot O, Catry-Thomas I, Taillandier L, Guillamo JS, Campello C, Monjour A, Cartalat-Carel S, Barrie M, Huchet A, Beauchesne P, Matta M, Mokhtari K, Tanguy ML, Honnorat J, Delattre JY. Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol. 2011 Aug 1;29(22):3050-5. doi: 10.1200/JCO.2011.34.8086. Epub 2011 Jun 27.

    PubMed 21709196

  • Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. doi: 10.1016/S1470-2045(14)70314-6. Epub 2014 Jul 15.

    PubMed 25035291

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.

    PubMed 15758009

  • Lou E, Peters KB, Sumrall AL, Desjardins A, Reardon DA, Lipp ES, Herndon JE 2nd, Coan A, Bailey L, Turner S, Friedman HS, Vredenburgh JJ. Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma. Cancer Med. 2013 Apr;2(2):185-95. doi: 10.1002/cam4.58. Epub 2013 Jan 24.

    PubMed 23634286

  • Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: 10.1200/JCO.2008.19.8721. Epub 2009 Aug 31.

    PubMed 19720927

  • Scott JG, Bauchet L, Fraum TJ, Nayak L, Cooper AR, Chao ST, Suh JH, Vogelbaum MA, Peereboom DM, Zouaoui S, Mathieu-Daude H, Fabbro-Peray P, Rigau V, Taillandier L, Abrey LE, DeAngelis LM, Shih JH, Iwamoto FM. Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older. Cancer. 2012 Nov 15;118(22):5595-600. doi: 10.1002/cncr.27570. Epub 2012 Apr 19.

    PubMed 22517216

  • Rosati G, Avallone A, Aprile G, Butera A, Reggiardo G, Bilancia D. XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study. Cancer Chemother Pharmacol. 2013 Jan;71(1):257-64. doi: 10.1007/s00280-012-2004-x. Epub 2012 Oct 26.

    PubMed 23100174

  • Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, Jonker D, Osborne S, Andre N, Waterkamp D, Saunders MP; AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1077-1085. doi: 10.1016/S1470-2045(13)70154-2. Epub 2013 Sep 10.

    PubMed 24028813

  • Biganzoli L, Di Vincenzo E, Jiang Z, Lichinitser M, Shen Z, Delva R, Bogdanova N, Vivanco GL, Chen Z, Cheng Y, Just M, Espie M, Vinholes J, Hamm C, Crivellari D, Chmielowska E, Semiglazov V, Dalenc F, Smith I. First-line bevacizumab-containing therapy for breast cancer: results in patients aged>/=70 years treated in the ATHENA study. Ann Oncol. 2012 Jan;23(1):111-118. doi: 10.1093/annonc/mdr043. Epub 2011 Mar 28.

    PubMed 21444356

  • Laskin J, Crino L, Felip E, Franke F, Gorbunova V, Groen H, Jiang GL, Reck M, Schneider CP. Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390). J Thorac Oncol. 2012 Jan;7(1):203-11. doi: 10.1097/JTO.0b013e3182370e02.

    PubMed 22173662

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temozolomide and Bevacizumab in people with Glioblastoma Multiforme and Primary Brain Tumor, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Overall Survival (OS) (time frame: OS calculated from the date of surgery until death or up to 36 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02898012, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2016.

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