NCT06419946

Brief Summary

Background: Glioblastoma (GBM) is notoriously difficult to treat, with current therapies often extending life by only a few months. The standard treatment involves surgery followed by radiation and chemotherapy with Temozolomide (TMZ). The efficacy of TMZ, however, is significantly enhanced when the tumor's o6-methylguanine-DNA-methyltransferase (MGMT) gene is methylated. Recent studies, such as the NOA-09 trial, have suggested that adding Lomustine (LOM) to TMZ could improve outcomes for patients with this specific tumor profile. Hypothesis: The investigators hypothesize that the addition of LOM to the TMZ regimen will lead to significantly improved survival rates among patients with newly diagnosed glioblastoma who have a methylated MGMT promoter compared to those receiving only TMZ. Treatment Plans: The study will randomly assign participants to two groups:

  • Control Group: Standard treatment with TMZ during and after radiation therapy.
  • Experimental Group: TMZ combined with LOM, starting on the first day of radiation therapy. Outcome Measures: The primary outcome measure will be survival. Other outcomes will include progression-free survival (time from randomization until tumor progression or death), safety profiles (adverse effects of the treatments), and quality of life measures as well as neurocognitive outcomes.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P25-P50 for phase_3

Timeline
93mo left

Started Feb 2025

Longer than P75 for phase_3

Geographic Reach
4 countries

20 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress14%
Feb 2025Dec 2033

First Submitted

Initial submission to the registry

April 29, 2024

Completed
18 days until next milestone

First Posted

Study publicly available on registry

May 17, 2024

Completed
9 months until next milestone

Study Start

First participant enrolled

February 1, 2025

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 15, 2031

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 15, 2033

Last Updated

April 13, 2026

Status Verified

March 1, 2026

Enrollment Period

6.9 years

First QC Date

April 29, 2024

Last Update Submit

April 7, 2026

Conditions

Glioblastoma, IDH-wildtypeMGMT-Methylated Glioblastoma

Keywords

precision medicinetemozolomidelomustineCCNUsurvival

Outcome Measures

Primary Outcomes (1)

  • overall survival

    visualized with Kaplan-Meier plot, tested with log-rank test

    Assessed from day of randomization to event or last day of follow-up (FU). Aanlyzed 36 months after last inclusion ensures that all patients have a potential of minimum 36 months FU

Secondary Outcomes (11)

  • progression free survival (PFS)

    Assessed from day of randomization to event or last day of follow-up (FU). Aanlyzed 36 months after last inclusion ensures that all patients have a potential of minimum 36 months FU

  • quality of life (QoL)

    done at baseline after informed consent, before randomisation and start of treatment, week 6 from start of treatment= end of radiotherapy, and every 24 weeks from start of treatment and for max 36 months.

  • neurocognition - verbal memory

    done at baseline after informed consent, before randomisation and start of treatment, week 6 from start of treatment= end of radiotherapy, and every 24 weeks from start of treatment and for max 36 months.

  • neurocognition - visual memory

    done at baseline after informed consent, before randomisation and start of treatment, week 6 from start of treatment= end of radiotherapy, and every 24 weeks from start of treatment and for max 36 months.

  • neurocognition - motor speed and fine motor control

    done at baseline after informed consent, before randomisation and start of treatment, week 6 from start of treatment= end of radiotherapy, and every 24 weeks from start of treatment and for max 36 months.

  • +6 more secondary outcomes

Study Arms (2)

treatment arm

EXPERIMENTAL

arm with temozolomide (TMZ) plus lomustine (LOM) treatment. 6 cycles of LOM/TMZ Start day 1 of RT. Cycle length of 42 days. Duration 9 months.

Drug: TemozolomideDrug: Lomustine

standard arm

ACTIVE COMPARATOR

arm with standard of care treatment with temozolomide only. Oral TMZ 75 mg/m2 daily during RT and with start day 1 of RT. This is followed by 6 cycles of TMZ with start 4 weeks after the end of RT. Cycle length 28 days. Duration 8,5 months.

Drug: Temozolomide

Interventions

TemozolomideDRUG

In the experimental treatment arm: a combination of Temozolomide and Lomustine, taken together, two separate pills

Also known as: TMZ
standard armtreatment arm
LomustineDRUG

In the experimental treatment arm: a combination of Temozolomide and Lomustine, taken together, two separate pills

Also known as: LOM
treatment arm

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed glioblastoma/gliosarcoma, IDH wild type
  • Methylated MGMT promoter
  • World Health Organization performance status 0-2
  • Age 18-70

You may not qualify if:

  • Previous malignancy within 3 y or malignancy treated non-curatively
  • Previous chemotherapy or radiotherapy involving the head
  • Off-protocol tumor-specific treatment
  • Serious comorbidity

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

University Hospital Graz

Graz, Austria

NOT YET RECRUITING

Medizinische Universität Innsbruck

Innsbruck, Austria

NOT YET RECRUITING

Kepler University Hospital

Linz, Austria

RECRUITING

University Hospital St. Pölten

Sankt Pölten, Austria

ENROLLING BY INVITATION

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Haukeland University Hospital

Bergen, Norway

RECRUITING

Sorlandet Sykehus

Kristiansand, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Stavanger University Hospital

Stavanger, Norway

NOT YET RECRUITING

St Olavs Hospital

Trondheim, Norway

NOT YET RECRUITING

Gävle Hospital

Gävle, Sweden

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Ryhov County Hospital

Jönköping, Sweden

RECRUITING

Kalmar Country Hospital

Kalmar, Sweden

RECRUITING

Skåne University Hospital

Lund, Sweden

NOT YET RECRUITING

Örebro University Hospital

Örebro, Sweden

RECRUITING

Karolinska Institutet

Stockholm, Sweden

ENROLLING BY INVITATION

Sundsvall Hospital

Sundsvall, Sweden

ENROLLING BY INVITATION

Norrlands Universitetssjukhus, Umea, Sweden

Umeå, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Related Publications (7)

  • 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.

    PMID: 15758009BACKGROUND

  • 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.

    PMID: 22877848BACKGROUND

  • Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. doi: 10.1056/NEJMoa043331.

    PMID: 15758010BACKGROUND

  • Weller M, Le Rhun E. How did lomustine become standard of care in recurrent glioblastoma? Cancer Treat Rev. 2020 Jul;87:102029. doi: 10.1016/j.ctrv.2020.102029. Epub 2020 May 4.

    PMID: 32408220BACKGROUND

  • Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

    PMID: 29260225BACKGROUND

  • Herrlinger U, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Sabel M, Hau P, Kortmann RD, Krex D, Grauer O, Goldbrunner R, Schnell O, Bahr O, Uhl M, Seidel C, Tabatabai G, Kowalski T, Ringel F, Schmidt-Graf F, Suchorska B, Brehmer S, Weyerbrock A, Renovanz M, Bullinger L, Galldiks N, Vajkoczy P, Misch M, Vatter H, Stuplich M, Schafer N, Kebir S, Weller J, Schaub C, Stummer W, Tonn JC, Simon M, Keil VC, Nelles M, Urbach H, Coenen M, Wick W, Weller M, Fimmers R, Schmid M, Hattingen E, Pietsch T, Coch C, Glas M; Neurooncology Working Group of the German Cancer Society. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet. 2019 Feb 16;393(10172):678-688. doi: 10.1016/S0140-6736(18)31791-4. Epub 2019 Feb 14.

    PMID: 30782343BACKGROUND

  • Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bahr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schafer N. Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2019 Oct;20(10):1444-1453. doi: 10.1016/S1470-2045(19)30502-9. Epub 2019 Sep 2.

    PMID: 31488360BACKGROUND

Related Links

MeSH Terms

Conditions

Glioblastoma

Interventions

TemozolomideLomustine

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

DacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNitrosourea CompoundsUreaAmidesNitroso Compounds

Study Officials

  • Annika Malmström, MD, PhD

    University Hospital, Linkoeping

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Asgeir S Jakola, MD, PhD

CONTACT

+46313429741asgeir.jakola@vgregion.se

Annika Malmström, MD. PhD

CONTACT

annika.malmstrom@regionostergotland.se

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Everyone: Radiotherapy (RT) consists of 60 Gy standard RT (RT 30x2Gy) Experimental treatment arm (TMZ/LOM): 6 cycles of LOM/TMZ Start day 1 of RT. Cycle length of 42 days. Duration 9 months. Standard treatment arm (TMZ): Oral TMZ 75 mg/m2 daily during RT and with start day 1 of RT. This is followed by 6 cycles of TMZ with start 4 weeks after the end of RT. Cycle length 28 days. Duration 8,5 months. Everyone: TTFields start with radiotherapy/chemotherapy - but only in Sweden where TTF is part of standard of care (SOC). Ongoing until 2nd progression or max 2 years.
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 29, 2024

First Posted

May 17, 2024

Study Start

February 1, 2025

Primary Completion (Estimated)

December 15, 2031

Study Completion (Estimated)

December 15, 2033

Last Updated

April 13, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Since the proposed randomized controlled trial (RCT) will be running for many year and since the investigators want to avoid outdated results, there will be - independent of the results of this proposed RCT - a collaboration to pool this study's data with the very similar phase 3 trial, the NOA-09 study. Here, the investigators will set a meta-analysis in place to balance clinical benefit with time and costs in a good manner. Hence, data is used for new sub-projects to endorse findings.

Locations

DK(1)NO(5)SE(10)AU(4)