losartan potassium for Glioblastoma|Brain metastases from non-small-cell lung cancer

Inclusion criteria

• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Organ functions of sufficient quality and robustness to undergo study treatment as determined by the study PI or designee"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Ability to understand and the willingness to sign a written informed consent document"}
• {"criterion_text":"- Ability to undergo an MRI exam, including administration of a standard clinical dose of an MRI-specific contrast agent of gadolinium or similar"}
• {"criterion_text":"- 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 – or – compromise more than 30 image voxels on perfusion MRI to ensure adequate parametric statistical assessments. For a perfusion MRI resolution of 1.2x1.2x5mm, this equals a tumor volume of 0.2 cubic centimeters (cc)."}
• {"criterion_text":"- Age ≥18 years"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- An ECOG performance status of ≤2 or equivalent KPS of ≥60%"}
• {"criterion_text":"- Life expectancy from start of treatment of more than 3 months"}
• {"criterion_text":"- Previous history of a neurosurgical procedure, at time of study inclusion (Study A only)"}
• {"criterion_text":"- 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 and/or stereotactic radiosurgery (Study B)"}

Exclusion criteria

• {"criterion_text":"- Hypersensitivity to the active substance (losartan) or to any of the excipients"}
• {"criterion_text":"- For Study B subjects only: A diagnosis of immunodeficiency or hypersensitivity to PD-1 inhibitors or any excipients."}
• {"criterion_text":"- 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 the treating physician"}
• {"criterion_text":"- Patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy"}
• {"criterion_text":"- Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study as determined by the treating physician"}
• {"criterion_text":"- Pregnant or breastfeeding patient"}
• {"criterion_text":"- Known additional active non-study related malignancy"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)"}
• {"criterion_text":"- Unable to undergo brain MRI according to study protocol"}
• {"criterion_text":"- Patients on antihypertensive agents that cannot be substituted with losartan."}
• {"criterion_text":"- Patients on medication that may induce hypotension and/or increase potassium levels and/or cause metabolismrelated 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."}
• {"criterion_text":"- Patients with hepatic or renal impairment of any reason"}
• {"criterion_text":"- Patients with symptomatic hypotension of any reason"}
• {"criterion_text":"- Patients with primary hyperaldosteronism"}
• {"criterion_text":"- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine"}
• {"criterion_text":"- Inadequate recovery from toxicity and/or complications of previous therapy as determined by the treating physician"}
• {"criterion_text":"- Patients with evidence of recurrence inside the radiotherapy target volume less than 3 months since last radiotherapy fraction (Study A – recurrent glioblastoma only)"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in the radiographic biomarker relative cerebral blood flow (rCBF) in the primary tumor area, and normalized to reference tissue [Time Frame: Study A (patients with recurrent glioblastoma) Baseline, Day 14-16, Day 28-30, Day 42-44.Study A (patients with newly diagnosed glioblastoma) Baseline, Day 14-16, Day 28-30, Day 42-44.tudy B (lung patients with metastases to the brain) Baseline, Day 90-14, Day 180-14, Day 270-14]","definition_or_measurement_approach":"Measured as change from baseline in relative cerebral blood flow (rCBF) in the primary tumor area normalized to reference tissue; time points specified per study cohort (Study A: Baseline, Day 14-16, Day 28-30, Day 42-44; Study B: Baseline, Day 90-14, Day 180-14, Day 270-14)."}
• {"endpoint_text":"- Change from baseline in the radiographic biomarker tissue stiffness, as derived from the shear wave modulus G of the MR-elastography readout in the primary tumor area, and normalized to reference tissue [Time Frame: Study A (patients with recurrent and newly diagnosed glioblastoma) Baseline, Day 14-16, Day 28-30, Day 42-44.Study B (lung patients with metastases to the brain) Baseline, Day 90-14, Day 180-14, Day 270-14]","definition_or_measurement_approach":"Measured as change from baseline in tissue stiffness using shear wave modulus G from MR-elastography in the primary tumor area normalized to reference tissue; time points specified per cohort (Study A and Study B timepoints as above)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in experimental radiographic biomarkers from MRI, including total volume of enhancing tumor, the total volume of tumor edema, perfusion MRI, diffusion MRI, or MR Elastography., and normalized to reference tissue.","definition_or_measurement_approach":"Measured as change from baseline in listed MRI-derived radiographic biomarkers normalized to reference tissue."}
• {"endpoint_text":"- Change from baseline in neurologic performance scores by Karnofsky Performance Score (KPS), Eastern Cooperative Oncology Group (ECOG) and/or Neurologic Assessment in Neuro- Oncology (NANO) scores.","definition_or_measurement_approach":"Measured as change from baseline in KPS, ECOG and/or NANO scores."}
• {"endpoint_text":"- Best overall response of radiographic status on MRIs of intracranial disease or corresponding treatment response by the Response Assessment in Neuro-Oncology (RANO) criteria. (occurrence of radionecrosis, pseudoprogression or tumor progression).","definition_or_measurement_approach":"Assessed by MRI using RANO criteria; includes tracking occurrences of radionecrosis, pseudoprogression or progression."}
• {"endpoint_text":"- Total dose and change in steroids dosage during study treatment duration.","definition_or_measurement_approach":"Recorded total steroid dose and change from baseline during treatment period."}
• {"endpoint_text":"- Change from baseline in the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ BN20) core 30 version 3.0.","definition_or_measurement_approach":"Patient-reported QOL measured by EORTC QLQ BN20/QLQ-C30 instruments; change from baseline recorded."}
• {"endpoint_text":"- Six-months progression free survival (6MPFS)","definition_or_measurement_approach":"Proportion of patients progression-free at six months."}
• {"endpoint_text":"- Progression free survival (PFS) [Time Frame: up to 24 months]","definition_or_measurement_approach":"Time from treatment start to disease progression or death, up to 24 months."}
• {"endpoint_text":"- Overall survival (OS) at 12 and 24 months","definition_or_measurement_approach":"Overall survival rates at 12 and 24 months post-treatment initiation."}
• {"endpoint_text":"- Overall survival [Time Frame: up to 24 months]","definition_or_measurement_approach":"Time from treatment start to death from any cause, up to 24 months."}
• {"endpoint_text":"- Drug tolerance of IMP (NCI-CTCAE v4.0) according to study and follow-up period, including number and frequency of losartan treatment emerging adverse events (TEAE), vital signs (, blood pressure, pulse) and conventional laboratory blood parameters.","definition_or_measurement_approach":"Safety assessed per NCI-CTCAE v4.0 including TEAE counts/frequency, vital signs and lab parameters."}
• {"endpoint_text":"- Change from baseline in experimental biomarkers from blood and serum, including vascular endothelial growth factors, angiopoietins, placental growth factors, epidermal growth factor receptors, hyaluronan levels, collagens levels, and inflammatory cytokines.","definition_or_measurement_approach":"Measured changes in listed blood/serum biomarkers from baseline."}

Norway

Earliest CTIS Part Ii Submission Date

08-08-2023

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

891

Number Of Sites

1

Number Of Participants

153

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway