Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)
NCT ID: NCT05112549
Last Updated: 2025-04-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
46 participants
INTERVENTIONAL
2021-10-12
2027-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
An Integrated Radio-immunological Approach
NCT05267509
Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base
NCT01182779
Multi-parametric Imaging in Personalized Radiotherapy
NCT05888064
Secondary Central Nervous System Lymphoma Registry - Charité
NCT05114330
Prospective Neurobehavioral Outcomes Follow-up in Primary CNS Lymphoma Patients Treated With Cranial Radiotherapy Combined With or Without MTX-based Chemotherapy According to the Multidisciplinary Treatment Guidelines Implemented at a Single Institute
NCT02655744
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SEQUENTIAL
For part I (3+3 Design) there will be four cohorts:
Cohort 1 with a fix dose of 20 mg, Cohort 2 with a fix dose of 30 mg, Cohort 3 with a fix dose of 40 mg and Cohort 4 with a fix dose of 50 mg.
The dosage in the expansion part II will be fixe dosage for all patients depending on the results from Part I
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
intrathecal Nivolumab
This is a prospective, interventional, open label, multicenter phase I trial in leptomeningeal disease in subjects with solid tumor that have a registered indication for intravenous treatment with PD1 antibody. Subject will undergo 6 cycles each 14 days in duration and a safety visit 7 days after the 3th dosage and 7 days after the 6th dosage. The Follow-up phase will start four weeks after the last dose and will continue monthly (up to 4 Follow-up visits in total).The study consists of two parts:
Part I "dose - escalation phase" (3 + 3 design) with 4 cohorts and each subject will receive an intrathecal nivolumab treatment with a fixed predefined dose (20 mg, 30 mg, 40 mg or 50 mg). On each dose level, exposure of subjects to intrathecal nivolumab will follow a staggered approach. Part II "dose expansion phase": subjects will receive an intrathecal PD1 treatment with a fixe dose, depending on the results from Part I.
Nivolumab [Opdivo]
Nivolumab (OPDIVO®) is a marketed pharmaceuticals material authorized in the European Union. This study uses an off-label route of administration of nivolumab. Subjects with leptomeningeal disease in solid tumours with an approved indication for intravenous treatment with the PD1 antibody will receive an intrathecal application of nivolumab. A total of six i.th. applications will be performed every 14 days. The intrathecal administration will be performed via an Ommaya reservoir or another intraventricular catheter.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Nivolumab [Opdivo]
Nivolumab (OPDIVO®) is a marketed pharmaceuticals material authorized in the European Union. This study uses an off-label route of administration of nivolumab. Subjects with leptomeningeal disease in solid tumours with an approved indication for intravenous treatment with the PD1 antibody will receive an intrathecal application of nivolumab. A total of six i.th. applications will be performed every 14 days. The intrathecal administration will be performed via an Ommaya reservoir or another intraventricular catheter.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Existing ability to understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
3. Patient is at "good risk" ( NCCN guidelines version 1.2021)
4. Existence of the following Tumor board protocol confirmations: clinical recommendation for intrathecal therapy and evaluation of trial enrolment \& statement on the potential necessity of additional systemic treatment of metastatic tumor outside the CNS
5. Existing ability to adhere to the study visit schedule and other protocol requirements
6. Existing agreement to refrain from donating blood while on study drug and for 30 days after discontinuation from this study treatment
7. Karnofsky performance score \> 50%
8. Diagnosis of LMD by CSF and/or MRI (details see Study protocol)
9. If radiation therapy was performed please confirm: Participants eligible for IT-PD1 should have completed their radiation therapy due to clinical indication \> 2 weeks prior to enrollment into the trial
10. Neurological examination (NANO scale) acc. Nayak et al., 2017 performed
11. MRI assessment at screening is based on the LANO scorecard acc. to Le Rhun et al., 2019
12. Existing ability to undergo intrathecal therapy via an intraventricular catheter (e.g. Ommaya reservoir)
13. Primary tumor tissue for the assessment of PD-1 and PD-L1 is optional at the timepoint of inclusion and enrollment but does need to be shipped before end of the trial.
14. Existing willingness of female patient of childbearing potential and male patient with female partner of childbearing potential to use highly effective contraceptive methods during treatment and for 150 days (male or female, see SmPC) after the last dose (details see Study protocol)
Exclusion Criteria
2. Previous intrathecal nivolumab application.
3. Patient at "poor risk" (NCCN guidelines version 1.2021)
5. History of hypersensitivity to monoclonal antibodies
6. Participation in other clinical AMG or MDR trials or observation period of competing trials or if there is otherwise a high risk of insurance law issues intervening between two studies and if the participation affects the primary endpoint of the IT-PD1 study. In case of uncertainty, competing insurances must be contacted prior to participation
7. A clinical condition that in the opinion of the investigator would interfere with the evaluation or interpretation of patient safety or trial results or that would prohibit the understanding of informed consent and compliance with the requirements of the protocol
8. Any treatment-related toxicities from prior systemic anti-tumor or immune therapy not having resolved to CTCAE version 5.0 grade 1, with the exception of alopecia
9. Patient with confirmed history of current autoimmune disease
10. Patients with any disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
11. Existence of clinically significant active infection (details see study protocol)
12. Inability to undergo MRI with contrast agent
13. The underlying primary tumor has not a registered and authorized indication in the European Union for intravenous treatment with Nivolumab, Pembrolizumab or Atezolizumab (details see study protocol). In addition, leptomeningeal disease of solid tumors with a high tumor mutational burden is also eligible.
14. Existence of abnormal laboratory values for the following values in hematology, coagulation parameters, liver and renal function (details see study protocol)
15. Patients who have received live or attenuated vaccine therapy used for prevention of infectious disease within 4 weeks of the first IT application of nivolumab
16. Patients requiring chronic systemic corticosteroid therapy (\> 10 mg prednisone or equivalent per day) or any other immunosuppressive therapies (including anti-TNF-a therapies)
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University Hospital Tuebingen
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Ghazaleh Tabatabai, Prof.Dr.
Role: STUDY_DIRECTOR
University Hospital Tuebingen
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Universitätsklinikum Bonn
Bonn, , Germany
University Hospital Freiburg, Neurosurgery
Freiburg im Breisgau, , Germany
University Hospital Heidelberg, Neurooncology
Heidelberg, , Germany
SLK-Kliniken Heilbronn GmbH Klinik
Heilbronn, , Germany
University Hospital Mannheim, Neurology Clinic
Mannheim, , Germany
Klinikum rechts der Isar/Technische Universität München
München, , Germany
Katharinenhospital Stuttgart
Stuttgart, , Germany
University Hospital Tübingen, Neurooncology
Tübingen, , Germany
University Hospital Ulm, ECTU - Early Clinical Trail Unit
Ulm, , Germany
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Ulrich Herrlinger, Prof. Dr.
Role: primary
Oliver Schnell, Prof. Dr.
Role: primary
Antje Wick, Dr.
Role: primary
Uwe Martens, Prof. Dr.
Role: primary
Michael Platten, Prof. Dr.
Role: primary
Denise Bernhardt, PD Dr.
Role: primary
Gerhard Illerhaus, Prof. Dr.
Role: primary
Regine Mayer-Steinacker, Dr.
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2021-001795-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
IT-PD1
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.