GlioblastomaPhase 2ImPRESSNCT03951142

Imaging Perfusion Restrictions From Extracellular Solid Stress - An Open-label Losartan Study

A Phase 2 study testing Losartan in people with Glioblastoma and Brain Metastases, run by Kyrre Eeg Emblem at 1 site in Norway.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

An open-label, single institutional phase II trial of losartan in patients with primary and metastatic brain tumors with an individual stepped-wedge, randomized, assessor-blinded, dose-finding design on three indications. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma, Brain Metastases
What is being tested?: Losartan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 165 participants
Where: 1 siteNorway
Study dates: 1 Oct 2019to 31 Dec 2024
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

A histologically confirmed intracranial glioblastoma, WHO grade 4 (Study A), or a minimum of one radiographically confirmed metastasis to the brain from a primary non-small-cell lung cancer (Study B)
Ability to undergo an MRI exam, including administration of a standard clinical dose of an MRI-specific contrast agent of gadolinium or similar
Measurable intracranial disease (Study A - recurrent glioblastoma, and Study B only), defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm with MRI
Age ≥18 years
Eligible for administration of the active substance (losartan) in concordance with study protocol, the criteria of the product label (Cozaar) and deemed fit for trial by the treating physician.
An ECOG performance status of ≤2 or equivalent KPS of ≥60%

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Life expectancy from start of treatment of more than 3 months
Previous history of neurosurgical procedure (Study A - only) or stereotactic radiosurgery and immunotherapy (Study B) at time of study inclusion
Scheduled for chemotherapy and/or radiotherapy and/or stereotactic radiosurgery (Study A - recurrent glioblastoma), neurosurgery, radiotherapy and chemotherapy (Study A - newly diagnosed glioblastoma), immunotherapy and/or chemotherapy (Study B)
Pre-study documentation on O6-methylguanin-DNA-methyltransferase (MGMT) promoter methylation status and on the isocitrate dehydrogenase (IDH) gene mutation status of their disease (study A only)
Organ functions of sufficient quality and robustness to undergo study treatment as determined by the study principal investigator (PI) or designee
Female patients of childbearing potential (postmenarcheal, not postmenopausal (>12 continuous months of amenorrhea with no identified cause other than menopause), and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing IMP treatment and for at least 14 days after the last dose. Birth control methods considered to be highly effective include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence when it is the preferred and usual lifestyle of the subject.
Ability to understand and the willingness to sign a written informed consent document

Who cannot join

Hypersensitivity to the active substance (losartan) or to any of the excipients
Patients on antihypertensive agents that cannot be substituted with losartan.
Patients on medication that may induce hypotension and/or increase potassium levels and/or cause metabolism-related pharmacokinetic drug-drug interactions with losartan. If medication with such effects can safely be discontinued or replaced, the patient can be included in the study after a washout period before baseline.
Patients with hepatic or renal impairment of any reason
Patients with symptomatic hypotension of any reason
Patients with primary hyperaldosteronism

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Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine
Inadequate recovery from toxicity and/or complications of previous therapy as determined by the treating physician
Patients with evidence of recurrence inside the radiotherapy target volume less than 3 months since last radiotherapy fraction (Study A - recurrent glioblastoma only)
For Study B subjects only. A diagnosis of immunodeficiency or hypersensitivity to the PD-1 inhibitors or any of its excipients
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, coronary heart disease and cerebrovascular disease, unstable angina pectoris, cardiac arrhythmia, angioedema, intravascular volume depletion, or psychiatric illness/social situations that would limit compliance with study requirements as determined by treating the physician
Patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy
Patient with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study as determined by the treating physician
Pregnant or breastfeeding patient
Known additional active non-study related malignancy
Applies to Study B patients qualifying for immunotherapy only: Active autoimmune disease that has required systemic treatment in the last 2 years (including use of non-study related disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed
Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Unable to undergo brain MRI according to study protocol
For Study B subjects only: No previous history of immunotherapy at time of study inclusion.

Trial locations and contacts

1 site in 1 country.

Norway1 site

Oslo University Hospital
Oslo, 0372

Other trials in Norway

About this study

Read the detailed description

For this study losartan, an angiotensin-II inhibitor, is defined as the Investigational Medicinal Product (IMP). The focus of the study is to assess the dose-response relationship of losartan on imaging-based measures of tissue perfusion and mechanical forces in patients with brain tumors. We hypothesize that losartan improves the effect of traditional cancer treatment by alleviating mechanical forces (solid stress) of the tumor microenvironment to improve tissue perfusion, while administration of losartan alone has little effect on cancer patients.

This is an open-label study and no active comparator or placebo will be used. Study participants include adult patients with newly diagnosed- and recurrent glioblastoma, as well as adult patients with metastatic brain tumors from non-small cell lung cancer. The study will assess the safety of losartan treatment and its dose-response relationship on conventional and experimental radiographic characteristics when used alone or as an add-on to standard cancer treatment.

Conditions: Glioblastoma, Brain Metastases
Being tested: Losartan
Keywords: Magnetic Resonance Imaging, Brain Cancer, Angiotensin II receptor blocker, Losartan, Perfusion, Solid stress
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.

LosartanDrug
This trial is open-label; therefore, the participant, the trial site personnel, the Sponsor and/or designee are not blinded to treatment. Drug identity (name, strength) is included in the label text. Storage, handling and preparation requirements will be handled in concordance with the Pharmacy Manual for losartan.

Study groups in NCT03951142
Study group	Role	What they receive
Study A: Recurrent glioblastoma (denoted 'AR')	Experimental	Patients with recurrent glioblastoma (N=54) with be randomized (ratio 1:1:1) to doses of 25mg, 50mg or 100mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 2 weeks (14 consecutive days) defined as a treatment cycle. Based on randomization, a minimum of three cycles and a maximum of 12 cycles will be administered for a total of 6 weeks (42 days) to 24 weeks (168 days), respectively. Patients randomized to 100mg of losartan will all receive treatment for the maximum duration. A stepped-wedge randomized design (ratio 1:1:1 for all doses over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving chemotherapy (temozolomide or lomustine tablets). Receives: Drug: Losartan
Study A: Newly diagnosed glioblastoma (denoted 'AN')	Experimental	Patients with newly diagnosed glioblastoma (N=54) with be randomized (ratio 1:1:1) to doses of 25mg, 50mg or 100mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 2 weeks (14 consecutive days) defined as a treatment cycle. Based on randomization, a minimum of three cycles and a maximum of 17 cycles will be administered for a total of 6 weeks (42 days) to 34 weeks (238 days), respectively. Patients randomized to 100mg of losartan will all receive treatment for the maximum duration. A stepped-wedge randomized design (ratio 1:1:1 for all doses over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving adjuvant chemotherapy (Temozolomide tablets). Receives: Drug: Losartan
Study B: Brain metastases (denoted 'BM')	Experimental	Patients with brain cancer from non-small cell lung cancer (N=45) with all receive a dose of 50mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 3 months (90 consecutive days) defined as a treatment cycle. A minimum of one cycle and a maximum of three cycles will be administered for a total of 3 months (90 days) to 9 months (270 days), respectively. A stepped-wedge randomized design (ratio 1:1:1 over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving chemotherapy alone (carboplatin in combination with vinorelbin or pemetrexed or equivalent analogs) or in combination with pembrolizumab (2mg/kg/3rd week). Receives: Drug: Losartan

What is being measured

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

Relative cerebral blood flow by MRI
Change from baseline in the radiographic biomarker relative cerebral blood flow (rCBF)
Measured: Study AR: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm BM: Baseline, Day 90±7, Day 180±7, Day 270±7
Relative solid stress by MRI
Change from baseline in the radiographic biomarker relative solid stress
Measured: Study AR: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm BM: Baseline, Day 90±7, Day 180±7, Day 270±7

Secondary outcomes (21)

Relative cerebral blood volume by MRI
Change from baseline in the radiographic biomarker relative cerebral blood volume (rCBV)
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Mean transit time by MRI
Change from baseline in the radiographic biomarker relative mean transit time (rMTT)
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Contrast agent extravasation by MRI
Change from baseline in the radiographic biomarker contrast agent extravasation
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative vessel size index by MRI
Change from baseline in the radiographic biomarker relative vessel size index
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative mean vessel density by MRI
Change from baseline in the radiographic biomarker relative mean vessel density
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative mean vessel caliber by MRI
Change from baseline in the radiographic biomarker relative mean vessel caliber
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Apparent diffusion coefficient by MRI
Change from baseline in the radiographic biomarker apparent diffusion coefficient
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Fractional anisotropy by MRI
Change from baseline in the radiographic biomarker fractional anisotropy
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative shear modulus by MRI
Change from baseline in the radiographic biomarker relative shear modulus
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative stiffness by MRI
Change from baseline in the radiographic biomarker relative stiffness
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative viscosity by MRI
Change from baseline in the radiographic biomarker relative viscosity
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative strain tensor by MRI
Change from baseline in the radiographic biomarker relative strain tensor
Measured: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Drug tolerance
Drug tolerance of losartan according to NCI-CTCAE v4.0
Measured: Study arm AR: Day 168+14. Study arm AN: Day 238+14. Study arm BM: Day 270+14.
Neurologic performance by KPS
Change from baseline in neurologic performance scores by Karnofsky Performance Score (KPS). Range from [00-0]. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Measured: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
Neurologic performance by ECOG
Change from baseline in neurologic performance scores by Eastern Cooperative Oncology Group (ECOG) scores. It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability in a range from 0 (best) to 5 (dead).
Measured: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
Neurologic performance by NANO
Change from baseline in neurologic performance scores by Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The NANO Scale evaluates 9 major domains of neurologic function, with each domain being scored on a range from 0 to 2 or 3.
Measured: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
RANO
Change from baseline in radiographic status on MRIs of intracranial disease corresponding to treatment response using the Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: Study arm AR: Day 78-8/+1, Day 162-8/+1. Study arm AN: Day 148-8/+1, Day 232-8/+1. Study arm BM: Day 90±14, Day 180±14, Day 270±14.
Steroid dosage
Change in dosage during study treatment.
Measured: Study arm AR: Baseline, Days 1-3, 29-31, 57±7, 85±7, 113±7, 141±7, 169±7. Study arm AN: Baseline, Days 29-31, 43-45, 71±7, 99±7, 127±7, 155±7, 183±7, 211±7, 239±7. Study arm BM: Baseline, Days 90±7, 180±7, 270±7, 360±7.
Quality of life (QoL)
Change from baseline in the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ BN20). It scores 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much."
Measured: Study arm AR: Baseline, Day 42-44, 169±4. Study arm AN: Baseline, Day 42-44, Day 155±4, Day 239±4. Study arm BM: Baseline, Day 90-7, Day 180-7, Day 270-7, Day 360±7
Progression free survival (PFS)
6-months progression free survival (6M-PFS) and within 2 years
Measured: All studies: Day +180, up to 24 months
Overall survival (OS)
12-months overall survival (12M-OS), 24-months overall survival (24M-OS) and within 2 years.
Measured: All studies: at 12 months, at 24 months, up to 24 months.

Timeline

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

1 Oct 201931 Dec 2024

First posted15 May 2019
Study start1 Oct 2019
Primary completion1 Oct 2024 (estimated)
Study completion31 Dec 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for GlioblastomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Model description: An open-label, single institutional phase II trial with an individual stepped-wedge, randomized, assessor-blinded, dose-finding design on three indications
Masking: None (open label)
Enrolment: 165 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03951142
Sponsor's protocol ID: ImPRESS
Other IDs: 2018-003229-27, 2018
Acronym: ImPRESS
Status last verified: Oct 2023
First submitted: 10 May 2019
Last updated: 1 Nov 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Study protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF) will be made available at the time of research data publication

Publications

Lysvik EK, Tulipan AJ, Haakensen VD, Revheim MR, Emblem KE, Hjornevik T. Quantitative [18F]PSMA-1007 PET in Treatment Response Monitoring of Brain Metastases from Non-small Cell Lung Cancer. Mol Imaging Biol. 2026 Jun;28(3):438-448. doi: 10.1007/s11307-026-02104-w. Epub 2026 Apr 23.
PubMed 42026421
Lysvik EK, Mikalsen LTG, Rootwelt-Revheim ME, Emblem KE, Hjornevik T. Optimization of Q.Clear reconstruction for dynamic 18F PET imaging. EJNMMI Phys. 2023 Oct 20;10(1):65. doi: 10.1186/s40658-023-00584-1.
PubMed 37861929

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Imaging Perfusion Restrictions From Extracellular Solid Stress - An Open-label Losartan Study
ClinicalTrials.gov ID: NCT03951142
Acronym / sponsor ID: ImPRESS / ImPRESS
Conditions: Glioblastoma, Brain Metastases
Keywords: Magnetic Resonance Imaging, Brain Cancer, Angiotensin II receptor blocker, Losartan, Perfusion, Solid stress
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 165 participants (estimated)
Lead sponsor: Kyrre Eeg EmblemUniversity, hospital or other
Study start: 1 Oct 2019 (actual)
Primary completion: 1 Oct 2024 (estimated)
Study completion: 31 Dec 2024 (estimated)
First posted: 15 May 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: An open-label, single institutional phase II trial with an individual stepped-wedge, randomized, assessor-blinded, dose-finding design on three indications

Arm	Type	Receives
Study A: Recurrent glioblastoma (denoted 'AR')	Experimental	Drug: LosartanPatients with recurrent glioblastoma (N=54) with be randomized (ratio 1:1:1) to doses of 25mg, 50mg or 100mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 2 weeks (14 consecutive days) defined as a treatment cycle. Based on randomization, a minimum of three cycles and a maximum of 12 cycles will be administered for a total of 6 weeks (42 days) to 24 weeks (168 days), respectively. Patients randomized to 100mg of losartan will all receive treatment for the maximum duration. A stepped-wedge randomized design (ratio 1:1:1 for all doses over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving chemotherapy (temozolomide or lomustine tablets).
Study A: Newly diagnosed glioblastoma (denoted 'AN')	Experimental	Drug: LosartanPatients with newly diagnosed glioblastoma (N=54) with be randomized (ratio 1:1:1) to doses of 25mg, 50mg or 100mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 2 weeks (14 consecutive days) defined as a treatment cycle. Based on randomization, a minimum of three cycles and a maximum of 17 cycles will be administered for a total of 6 weeks (42 days) to 34 weeks (238 days), respectively. Patients randomized to 100mg of losartan will all receive treatment for the maximum duration. A stepped-wedge randomized design (ratio 1:1:1 for all doses over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving adjuvant chemotherapy (Temozolomide tablets).
Study B: Brain metastases (denoted 'BM')	Experimental	Drug: LosartanPatients with brain cancer from non-small cell lung cancer (N=45) with all receive a dose of 50mg daily of losartan while on treatment. Losartan (tablet) will be administered every day, with 3 months (90 consecutive days) defined as a treatment cycle. A minimum of one cycle and a maximum of three cycles will be administered for a total of 3 months (90 days) to 9 months (270 days), respectively. A stepped-wedge randomized design (ratio 1:1:1 over the three first cycles) is proposed to compare participants on- and off- study IMP and assess any dose-response relationship losartan. This study arm will also investigate any additional long-term beneficial effects of losartan while receiving chemotherapy alone (carboplatin in combination with vinorelbin or pemetrexed or equivalent analogs) or in combination with pembrolizumab (2mg/kg/3rd week).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

A histologically confirmed intracranial glioblastoma, WHO grade 4 (Study A), or a minimum of one radiographically confirmed metastasis to the brain from a primary non-small-cell lung cancer (Study B)
Ability to undergo an MRI exam, including administration of a standard clinical dose of an MRI-specific contrast agent of gadolinium or similar
Measurable intracranial disease (Study A - recurrent glioblastoma, and Study B only), defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm with MRI
Age ≥18 years
Eligible for administration of the active substance (losartan) in concordance with study protocol, the criteria of the product label (Cozaar) and deemed fit for trial by the treating physician.

Key exclusion criteria (19 listed)

Hypersensitivity to the active substance (losartan) or to any of the excipients
Patients on antihypertensive agents that cannot be substituted with losartan.
Patients on medication that may induce hypotension and/or increase potassium levels and/or cause metabolism-related pharmacokinetic drug-drug interactions with losartan. If medication with such effects can safely be discontinued or replaced, the patient can be included in the study after a washout period before baseline.
Patients with hepatic or renal impairment of any reason
Patients with symptomatic hypotension of any reason

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LosartanThis trial is open-label; therefore, the participant, the trial site personnel, the Sponsor and/or designee are not blinded to treatment. Drug identity (name, strength) is included in the label text. Storage, handling and preparation requirements will be handled in concordance with the Pharmacy Manual for losartan.	Drug	Study A: Newly diagnosed glioblastoma (denoted 'AN'), Study A: Recurrent glioblastoma (denoted 'AR'), Study B: Brain metastases (denoted 'BM')

Primary outcome

Relative cerebral blood flow by MRI
Time frame: Study AR: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm BM: Baseline, Day 90±7, Day 180±7, Day 270±7
Change from baseline in the radiographic biomarker relative cerebral blood flow (rCBF)
Relative solid stress by MRI
Time frame: Study AR: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm BM: Baseline, Day 90±7, Day 180±7, Day 270±7
Change from baseline in the radiographic biomarker relative solid stress

21 secondary outcomes

Relative cerebral blood volume by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Mean transit time by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Contrast agent extravasation by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative vessel size index by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative mean vessel density by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative mean vessel caliber by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Apparent diffusion coefficient by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Fractional anisotropy by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative shear modulus by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative stiffness by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative viscosity by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Relative strain tensor by MRI
Time frame: Study arm AR: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 78-8/+1, Day 162-8/+1. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44, Day 148-8/+1, Day 232-8/+1. Study arm BM: Baseline, Day 90±14, Day 180±14, Day 270±14.
Drug tolerance
Time frame: Study arm AR: Day 168+14. Study arm AN: Day 238+14. Study arm BM: Day 270+14.
Neurologic performance by KPS
Time frame: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
Neurologic performance by ECOG
Time frame: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
Neurologic performance by NANO
Time frame: Study arm AR: Baseline, Day 14-16, Day 42-44, Day 85±4, Day 169±4. Study arm AN: Baseline, Day 14-16, Day 42-44, DAy 71±4, Day 155±4, Day 239±. Study arm BM: Baseline, Day 90-7, Day 180-1, Day 270-1, Day 360±7
RANO
Time frame: Study arm AR: Day 78-8/+1, Day 162-8/+1. Study arm AN: Day 148-8/+1, Day 232-8/+1. Study arm BM: Day 90±14, Day 180±14, Day 270±14.
Steroid dosage
Time frame: Study arm AR: Baseline, Days 1-3, 29-31, 57±7, 85±7, 113±7, 141±7, 169±7. Study arm AN: Baseline, Days 29-31, 43-45, 71±7, 99±7, 127±7, 155±7, 183±7, 211±7, 239±7. Study arm BM: Baseline, Days 90±7, 180±7, 270±7, 360±7.
Quality of life (QoL)
Time frame: Study arm AR: Baseline, Day 42-44, 169±4. Study arm AN: Baseline, Day 42-44, Day 155±4, Day 239±4. Study arm BM: Baseline, Day 90-7, Day 180-7, Day 270-7, Day 360±7
Progression free survival (PFS)
Time frame: All studies: Day +180, up to 24 months
Overall survival (OS)
Time frame: All studies: at 12 months, at 24 months, up to 24 months.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
Derived from this study: PubMed 42026421Lysvik EK, Tulipan AJ, Haakensen VD, Revheim MR, Emblem KE, Hjornevik T. Quantitative [18F]PSMA-1007 PET in Treatment Response Monitoring of Brain Metastases from Non-small Cell Lung Cancer. Mol Imaging Biol. 2026 Jun;28(3):438-448. doi: 10.1007/s11307-026-02104-w. Epub 2026 Apr 23.
Derived from this study: PubMed 37861929Lysvik EK, Mikalsen LTG, Rootwelt-Revheim ME, Emblem KE, Hjornevik T. Optimization of Q.Clear reconstruction for dynamic 18F PET imaging. EJNMMI Phys. 2023 Oct 20;10(1):65. doi: 10.1186/s40658-023-00584-1.
Individual participant dataSharing planned: Yes. Study protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF) will be made available at the time of research data publication

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Petter Brandal, MD, PhD principal investigator

Oslo University Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Losartan in people with Glioblastoma and Brain Metastases, run by Kyrre Eeg Emblem at 1 site 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 13 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 1 Nov 2023. 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 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 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?

Results are not available in the source record.

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?

Relative cerebral blood flow by MRI (time frame: Study AR: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm AN: Baseline, Day 14-16, Day 28-30, Day 42-44. Study arm BM: Baseline, Day 90±7, Day 180±7, Day 270±7). The study lists 2 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 NCT03951142, 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 1 Nov 2023.