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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05112549
Other study ID # IT-PD1
Secondary ID 2021-001795-42
Status Recruiting
Phase Phase 1
First received
Last updated
Start date October 12, 2021
Est. completion date September 30, 2026

Study information

Verified date December 2023
Source University Hospital Tuebingen
Contact Ghazaleh Tabatabai, Prof.Dr.
Phone +49 (0) 7071 - 2985018
Email ghazaleh.tabatabai@uni-tuebingen.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To determine the safety of intrathecal (IT) PD1 antibody for Intrathecal application of PD1 antibody in metastatic solid tumors with leptomeningeal disease of solid tumors.


Description:

Leptmeningeal disease (LMD) is an aggressive subtype of metastatic disease in the central nervous system (CNS) and has a poor prognosis with a median overall survival of a few months.The IT-PD1 trial group wants to contribute to an improvement of this situation for LMD patients by using an intrathecal application route for the PD1 antibody, i.e. a drug that has shown clinical efficacy in the underlying tumor via the intravenous route.


Recruitment information / eligibility

Status Recruiting
Enrollment 46
Est. completion date September 30, 2026
Est. primary completion date September 30, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Main Inclusion Criteria: 1. Patient aged = 18 years at the time of signing the informed consent 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) Main Exclusion Criteria: 1. Women during pregnancy and lactation. 2. Previous intrathecal nivolumab application. 3. Patient at "poor risk" (NCCN guidelines version 1.2021) 4. The following differential diagnoses to LMD are exclusion criteria: a. Aseptic, meningitis b. Viral meningitis, c. Bacterial meningitis 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Germany Universitätsklinikum Bonn Bonn
Germany University Hospital Freiburg, Neurosurgery Freiburg
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

Sponsors (1)

Lead Sponsor Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Assessment of Adverse Events for Dose Limiting Toxicities [Safety and Tolerabillity] This trial will investigate the maximum tolerable dose and safety of intrathecal PD1 antibody administration in LMD of metastatic solid tumors with a registered indication for treatment with intravenous PD1 antibody or PD-1L antibody. The safety endpoints will be assessed by a review of adverse events and serious adverse events according to CTCAE up to 4 months days after last dose.Subjects 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 appropriate dose for the expansion phase (Part II) is based on the results in Part I (dose escalation phase) and will define the maximum tolerable fix dose in Part II. up to 4 months after last dose
Secondary Overall Survival The secondary endpoint is overall survival defined as the time interval from the date of first study administration to the date of progression. last follow-up, up to 4 months after last dose
See also
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Active, not recruiting NCT03719768 - Avelumab With Radiotherapy in Patients With Leptomeningeal Disease Phase 1
Not yet recruiting NCT06146010 - Non Interventional German Leptomeningeal Disease Register
Active, not recruiting NCT03501979 - Tucatinib, Trastuzumab, and Capecitabine for the Treatment of HER2+ LMD Phase 2
Recruiting NCT05800275 - Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients With Leptomeningeal Disease Phase 2
Recruiting NCT04588545 - Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease Phase 1/Phase 2
Recruiting NCT05809752 - A First in Human Dose Escalation of Dendritic Cell Vaccine (DCV) Phase 1