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GlioblastomaPhase 1/2BORTEM-17NCT03643549

Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter (BORTEM-17)

A Phase 1/2 study testing Bortezomib and Temozolomide Phase IB and Bortezomib and Temozolomide Phase II in people with Glioblastoma, run by Haukeland University Hospital at 2 sites in Norway.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase IB/II trial is designed to investigate the safety and survival benefits for patients with recurrent grade-4 with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
Bortezomib and Temozolomide Phase IB and Bortezomib and Temozolomide Phase II
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
2 sitesNorway
Study dates
30 Aug 2018to 31 Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Life expectancy > 8 weeks
  • Histologically confirmed intracranial glioblastoma (GBM), with MGMT unmethylated promoter
  • Must submit an unstained paraffin block and/ or cryopreserved tumour tissue from surgical procedure
  • Radiologically (MRI) confirmed tumour relapse/progression ≥ 12 weeks since completed radiotherapy
  • Measurable recurrent tumor
  • Tumor not available for radio-surgery
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  • If previously treated with gammaknife, at least one evaluable lesion outside the irradiated area is required, unless the time after the radiosurgery is 12 weeks or more
  • Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure.
  • Karnofsky performance status ≥ 70
  • WBC ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • Bilirubin < 2.5 times upper limit of normal (ULN)
  • serum aspartate aminotransferase (AST) < 2.5 times ULN
  • Estimated GFR ≥ 60 mL/minute
  • Serum sodium > 130 mmol/L
  • Serum potassium level within normal limit
  • Stable or reduced doses of corticosteroids for at least 1 week prior to enrolment
  • Negative pregnancy test no longer than 14 days prior to enrollment
  • Fertile patients and female partners with child bearing potential of male patients must use adequate contraception
  • Patients on EIAED must be transitioned to non-EAIED for ≥ 2 weeks
  • Unfractionated and/or low molecular weight heparin allowed
  • Patients previously treated with neurosurgery er eligible for the study

Who cannot join

  • Hypersensitivity to Bortezomib, boron, or mannitol
  • Any contraindications for use of temozolomide
  • Peripheral neuropathy ≥ grade 2
  • Previous treatment with bevacizumab or lomustine alone or as a combination therapy for ralapsed glioblastoma (PCV as primary treatment of low grade glioma, before development of glioblastoma, is allowed)
  • Myocardial infarction within the past 6 months
  • NYHA class III or IV heart failure
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  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Known heart failure
  • Serious medical or psychiatric illness that would interfere with the study participation including, but not limited to, any of the following:
  • Ongoing or active infection requiring IV antibiotics
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus)
  • History of stroke within the past 6 months
  • Other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e., cervical cancer), or low-risk prostate cancer after curative therapy
  • Significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • Disease that will obscure toxicity or dangerously alter the drug metabolism
  • Viral hepatitis (HBV surface antigen positive) or active hepatitis C infection
  • Other investigational drugs must be stopped at least 12 weeks prior to therapy or treatment failure under other experimental therapy must be confirmed before study entry. If progression during other experimental therapy is confirmed, the time interval between previous treatment and BORTEM-17 may be reduced to 4 weeks
  • Concurrent inducers of CYP450 3A4 (e.g., enzyme-inducing anti-epileptic drugs [EIAED])

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Dorota Goplen, MD, PhD contact

+47 55974019

dgop@helse-bergen.no

Martha E Chekenya, PhD, Dr. Philos contact

+47 55586380

martha.enger@uib.no

Norway2 sites, 2 recruiting

  • Haukeland University Hospital

    Bergen, 5021

    Dorota Goplen, MD, PhD, +4755974019, dgop@helse-bergen.no

    Jorunn Brekke, MD, +4755970986, joub@helse-bergen.no

    Recruiting

  • Oslo University Hospital

    Oslo, 0424

    Petter Brandal, MD, pebra@ous-hf.no

    Recruiting

Other trials in Norway

About this study

Official title: Bortezomib Sensitization of Recurrent Grade-4 Glioma With Unmethylated MGMT Promoter to Temozolomide Phase 1B/II Study

This phase IB/II trial is designed to investigate the safety and survival benefits for patients with recurrent grade-4 with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule.

Read the detailed description

Patients harbouring tumours with functional O6 methylguanine DNA methyltransferase (MGMT) DNA repair enzyme efficiently repair the DNA damage inflicted by Temozolomide and gain limited benefit from this chemotherapy. Bortezomib depletes the MGMT enzyme, restoring the tumour´s susceptibility to Temozolomide, if the chemotherapy is administered in the precise schedule when the MGMT enzyme is depleted. Additionally, Bortezomib inhibits the growth of tumour cells by blocking autophagy flux. Temozolomide causes genotoxic stress in cancer cells that in turn respond by inducing protective processes such as autophagy. If both autophagy and MGMT DNA repair enzyme are blocked a priori, the efficacy of Temozolomide will be enhanced. Thus, pre-treating the tumour with Bortezomib prior to administration of Temozolomide leads to DNA repair enzyme depletion and blockade of autophagy-induced survival signals. The combined effect will sensitize the tumour to therapy, improve chemotherapy efficacy and prolong patient survival outcomes.

Hypothesis: Pretreatment with Bortezomib administered prior to Temozolomide will sensitize recurrent GBM with unmethylated MGMT promoter to standard TMZ in palliative setting.

Objective:

  • Assessment of safety and tolerability of Bortezomib administered with Temozolomide.
  • Determining the optimal dose of TMZ, when administered as combination therapy
  • Estimate the progression free survival (PFS) and overall survival (OS) of patients with recurrent or progressed glioblastoma after pre-treatment with Bortezomib prior to combination with Temozolomide.

Key secondary objectives

  • Tumour response to the therapy assessed by RANO and NANO criteria
  • Determine physiological, molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses.
Conditions
Glioblastoma
Being tested
Bortezomib and Temozolomide Phase IB, Bortezomib and Temozolomide Phase II
Keywords
Temozolomide, Bortezomib, Recurrent disease
Medical subject headings
Glioblastoma, Recurrence

What participants receive

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

  • Bortezomib and Temozolomide Phase IBDrug

    In the Phase IB of the study the following dose escalation of TMZ will be performed: The first cohort of 3 patients will receive 150 mg/m2 of IMP (TMZ) for 5 days q4w. If one patient in this cohort develops a dose limiting toxicity, another cohort of 3 patients will be treated at the same dose level until 2 or more patients in the group of 3-6 develop DLT.

  • Bortezomib and Temozolomide Phase IIDrug

    The patientes will be treated with the maximum recommended starting dose of Temozolomide and Bortezomib established in the IB phase of the study

Study groups in NCT03643549
Study groupRoleWhat they receive
Bortezomib and TemozolomideExperimentalBotezomib 1.3 mg/m2 administered IV on days 1, 4, 7, during each 4-week chemotherapy cycle with per oral Temozolomide at three dose levels: 150 mg/m2, 175 mg/m2 and 200mg/m2 5 days/week every 4 weeks starting on day 3.
Receives: Drug: Bortezomib and Temozolomide Phase IB; Drug: Bortezomib and Temozolomide Phase II

What is being measured

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

  1. Bortezomib-Temozolomide Maximum tolerated dose

    En intra- and inter-patient dose escalation period of TMZ administered after Bortezomib

    Measured: 6 months

  2. Overall survival

    Overall survival at 1 year

    Measured: 1 year

  3. Progression free survival

    Progression free survival at 6 months

    Measured: 6 months

  4. Time to progression

    Median time

    Measured: 4 years

Secondary outcomes (4)

  1. Biomarkers of treatment response

    Identification of novel tumor biomarkers by determining physiological, molecular and biochemical changes in blood and tumor tissue that correlate with treatment responses

    Measured: 4 years

  2. Tumour responses

    Assessed by contrast enhanced MRI according to RANO criteria

    Measured: 4 years

  3. Clinical response

    Assessment of the neurologic status according to NANO criteria

    Measured: 4 years

  4. Toxicity assessment

    SAE, all grades hematologic and non hematologic toxicity

    Measured: 4 years

Timeline

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

  1. First posted22 Aug 2018
  2. Study start30 Aug 2018
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Botezomib 1.3mg/m2 administered IV on days 1, 4, 7, during each 4-week chemotherapy cycle with per oral Temozolomide at three dose levels: 150 mg/m2, 175 mg/m2 and 200mg/m2 5 days/week every 4 weeks starting on day 3 until disease progression and/or unacceptable toxicity. Study group will be compared to historical controls on conventional management
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03643549
Sponsor's protocol ID
2017/2084
Acronym
BORTEM-17
Status last verified
Jun 2026
First submitted
21 Aug 2018
Last updated
4 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Goplen D, Rahman MA, Brekke J, Waha A, Oltedal L, Haasz J, Kumar S, Birkeland E, Selheim F, Lie SA, Chekenya M. Contrasting molecular and pharmacodynamic signatures of response and resistance to sequential bortezomib and temozolomide in recurrent IDH-wildtype glioblastoma and grade 4 IDH-mutant astrocytoma: an exploratory interim analysis of NCT03643549 phase IB/II trial. Biomark Res. 2026 Oct 27;14(1):148. doi: 10.1186/s40364-026-01023-w.

    PubMed 42947166

  • Rahman MA, Brekke J, Arnesen V, Hannisdal MH, Navarro AG, Waha A, Herfindal L, Rygh CB, Bratland E, Brandal P, Haasz J, Oltedal L, Miletic H, Lundervold A, Lie SA, Goplen D, Chekenya M. Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study. Immun Inflamm Dis. 2020 Sep;8(3):342-359. doi: 10.1002/iid3.315. Epub 2020 Jun 24.

    PubMed 32578964

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bortezomib and Temozolomide Phase IB and Bortezomib and Temozolomide Phase II in people with Glioblastoma, run by Haukeland University Hospital at 2 sites in Norway.

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 24 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: looking for participants now, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Norway. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

This study is still under way. Results are not available in the source record yet.

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

Contact Dorota Goplen, MD, PhD (+47 55974019, dgop@helse-bergen.no), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bortezomib-Temozolomide Maximum tolerated dose (time frame: 6 months). The study lists 4 primary outcomes in all. 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 NCT03643549, which also lists 2 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 4 Aug 2026.

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