Combined Intrathecal and Systemic Therapy With Trastuzumab Rezetecan for Leptomeningeal Metastases
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJiuda Zhao
About this trial
This phase II clinical study enrolls patients with leptomeningeal metastases from solid tumors. Participants will receive intrathecal and systemic administration of Trastuzumab Rezetecan. The study aims to obtain clinical evidence about the efficacy and safety of this antibody-drug conjugate (ADC) given via intrathecal plus systemic routes. It hopes to offer a new treatment option for these patients with hard-to-manage disease and provide scientific support for optimizing treatment strategies for solid tumor patients with leptomeningeal metastases.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged ≥ 18 years of any gender; histologically confirmed solid tumor; signed informed consent form.
Patients with Type I LMD (defined as positive cerebrospinal fluid cytology or positive leptomeningeal biopsy) or Type II LMD (diagnosed based on clinical manifestations and neuroimaging alone) according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) clinical practice guidelines;patients with treatment-naive LMD or recurrent LMD after radiotherapy.
Investigators assess that immediate radiotherapy for leptomeningeal lesions is not required, or the patient declines radiotherapy.
Expected survival ≥ 6 weeks.
Disqualifiers
Presence of severe central nervous system (CNS) complications, such as progressive cerebral edema; recurrent seizures refractory to standardized antiepileptic therapy. Note: "refractory recurrent seizures" refers to persistent clinical seizures despite adequate standardized antiepileptic treatment. Subjects with a prior history of epilepsy with long-term seizure control on medication are not excluded by this criterion.
Receipt of whole-brain radiotherapy or other intrathecal therapies within the recent 4 weeks, which may interfere with efficacy assessment.
History of active interstitial lung disease (ILD) or pneumonia.
History of allergy or hypersensitivity to the study drug or its components.
Trial design
Design model
Single group
Treatments tested in this trial
Intrathecal and systemic administration of Trastuzumab Rezetecan
DrugTrastuzumab-rezetecan is administered via combined intrathecal and systemic routes. Systemic dosing: 4.8 mg/kg by intravenous infusion once every 3 weeks (q3w). Intrathecal dosing: 20% of the systemic dose, administered once weekly during Cycle 1 and Cycle 2, then once every 3 weeks from Cycle 3 onward.
Treatment groups
28 Participants
are divided into 1 treatment groupGroup A: HER2 statusExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
3-month Overall Survival Rate
3-month overall survival (OS) rate is defined as the percentage of all enrolled participants who are still alive at 3-months from the date of receiving study treatment.
Time frame
3-months from the date of receiving study treatmentSecondary outcomes
1
Leptomeningeal Metastasis-Progression-Free Survival (LM-PFS)
Time from treatment initiation to the first documentation of leptomeningeal metastasis progression (based on neurological examination, cerebrospinal fluid testing, or neuraxis MRI) or death from any cause, whichever occurs first, in patients with solid tumor-associated leptomeningeal metastasis receiving intrathecal plus intravenous Trastuzumab Rezetecan.
Time frame
From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.2
Leptomeningeal Metastasis-Objective Response Rate (LM-ORR)
LM-ORR corresponds to Best Overall Response. It is not a single time-point assessment, but the best leptomeningeal metastasis therapeutic response documented from treatment initiation up to disease progression, study discontinuation, death, or pre-specified maximum follow-up.
Time frame
From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.3
Cerebrospinal Fluid Cytology Conversion Rate
For intrathecal treatment: Trastuzumab rezetecan is administered intrathecally once weekly in Cycle 1 and Cycle 2; starting from Cycle 3 and thereafter, intrathecal Trastuzumab rezetecan is given once per 3-week cycle. The cerebrospinal fluid cytology conversion rate is preliminarily evaluated after 6-week intrathecal treatment. Sustained absence of tumor cells in cerebrospinal fluid at this time point is defined as cerebrospinal fluid conversion to negative. The cerebrospinal fluid cytology conversion rate is calculated as: (Number of patients with negative cerebrospinal fluid tumor cells at 6-week post-treatment ÷ Total number of treated patients with leptomeningeal metastasis) × 100%
Time frame
6 weeks after initiation of intrathecal study treatment4
Extracranial Objective Response Rate (EC-ORR)
EC-ORR is defined as the percentage of patients whose best overall response of extracranial lesions is complete response (CR) or partial response (PR). Tumor assessments are performed per RECIST version 1.1from the date of first study treatment until study discontinuation secondary to disease progression.
Time frame
From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Jiuda Zhao
Lead sponsor
Affiliated Hospital of Qinghai University
Sponsor institution
The First Affiliated Hospital of Lanzhou Medical University
Collaborator
Xi'an International Medical Center Hospital
Collaborator
Shandong Cancer Hospital and Institute
Collaborator
Source ClinicalTrials.gov
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