Screening for Brain Metastases

Official title

Quality and Safety of Screening for Brain Metastases by Gadopiclenol in Patients With Cancer at High Risk of Developing Brain Metastases

Overview

The survival of patients with CNS metastases often remains limited to some months. CNS metastases are also associated with neurological decline and decrease of quality of life. An early identification of CNS metastases may potentially lead to more therapeutic options and prevent or delay the development of neurological symptoms and signs. Patients with cancer associated with a high risk of developing CNS metastasis will be enrolled in this trial. These patients are candidates for a screening brain MRI program in the routine management as recommended in current guidelines (Le Rhun et al. 2021) (Amaral et al. 2025, "ESMO Living Guideline: Cutaneous Melanoma, v1.0 February 2025"). The primary objective is to compare the time to CNS metastases diagnosis detected by MRI using different contrast agents (of gadopiclenol at a dose of 0.1 mmol/kg over current standard practice ) in patients with cancer considered at high risk of developing brain metastases.

Interventions

• Other gadopiclenol (contrast agent)
  Gadopiclenol is a contrast agent approved in Switzerland. In this study, a double-dose of gadopiclenol will be used: 0.2 mL body weight (equivalent to 0.1 mmol/kg BW) at the time of the screening brain MRI.
• Other standard contrast agent
  as per local standard of care

Primary outcome measures

• Time interval between enrolment and diagnosis of CNS metastases [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]

Secondary outcome measures (7)

• Incidence of CNS metastases [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]
• Assessment of the type of CNS metastases at the time of CNS event [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]
• Description of the neurological assessment [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]
• Assessment of the rate of diagnostic procedures triggered by the results and the rate of modifications of therapeutic decision making [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]
• Safety and tolerability 1 [Time frame: from randomization until one month after diagnosis of CNS metastasis event or up to a maximum of 25 months (one month after last MRI)]
• Safety and tolerability 2 [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]
• Qualitative assessment of images by the neuroradiologist [Time frame: from randomization until diagnosis of CNS metastasis event or up to a maximum of 24 months]

Eligibility criteria

Inclusion criteria

• Patients with histologically confirmed HER-2 positive or triple negative breast cancer, non-small cell lung cancer, or melanoma
• Up to 3 months after diagnosis of a cancer at high risk of CNS metastasis with indication for screening and follow-up by MRI (based on a high risk of CNS metastases according to EANO ESMO brain metastases guidelines: stage IV HER-2 positive or triple negative breast, stage II to IV lung cancer, stage IV melanoma)
• Enrolment at the time of initiation of screening and follow-up MRI: usually, but not necessarily at the time of new diagnosed stage IV HER-2 positive or triple negative breast, lung cancer, melanoma
• 18 years or older on day of signing informed consent
• Karnofsky performance status (KPS) ≥ 60
• Patients must have preserved renal function (serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 30 mL/min (using the Cockcroft-Gault formula)
• Women of child-bearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test before the MRI.
• Patients of childbearing / reproductive potential must agree to use adequate birth control measures, as defined by the investigator, during the study period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
• Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Exclusion criteria

• Any contraindication to MRI, including claustrophobia
• Known severe adverse drug reaction or contraindication to gadolinium-based contrast agents
• Acute or chronic renal insufficiency: grade III or more (eGFR <60 mL/min/1.73 m2) based on one eGFR assessment performed within one day the MRI prior to the first contrast agent injection.
• Heart failure: class III/IV NYHA
• Severe liver disease
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Women who are pregnant or who breast feeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Screening

Study locations

Switzerland · 1 center

• University Hospital Zurich — Zurich

Publications

• Le Rhun E, Guckenberger M, Smits M, Dummer R, Bachelot T, Sahm F, Galldiks N, de Azambuja E, Berghoff AS, Metellus P, Peters S, Hong YK, Winkler F, Schadendorf D, van den Bent M, Seoane J, Stahel R, Minniti G, Wesseling P, Weller M, Preusser M; EANO Executive Board and ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. EANO-ESMO Clinical Practice Guidelines for diagnosis, PMID 34364998
• Bendszus M, Roberts D, Kolumban B, Meza JA, Bereczki D, San-Juan D, Liu BP, Anzalone N, Maravilla K. Dose Finding Study of Gadopiclenol, a New Macrocyclic Contrast Agent, in MRI of Central Nervous System. Invest Radiol. 2020 Mar;55(3):129-137. doi: 10.1097/RLI.0000000000000624. PMID 31917762

Identifiers

NCT: NCT07492121 · GAPIMET

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗