Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease

• Status: Recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Tuebingen
• Treatments: Nivolumab

Criteria

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 available

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 trials or observation period of competing trials

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)

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)