RecruitingPhase 1NCT05112549

Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)

Sponsor

University Hospital Tuebingen

Enrollment

46 participants

Start Date

Oct 12, 2021

Study Type

INTERVENTIONAL

Conditions

Leptomeningeal Disease

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

Patient aged ≥ 18 years at the time of signing the informed consent
Existing ability to understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
Patient is at "good risk" ( NCCN guidelines version 1.2021)
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
Existing ability to adhere to the study visit schedule and other protocol requirements
Existing agreement to refrain from donating blood while on study drug and for 30 days after discontinuation from this study treatment
Karnofsky performance score > 50%
Diagnosis of LMD by CSF and/or MRI (details see Study protocol)
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
Neurological examination (NANO scale) acc. Nayak et al., 2017 performed
MRI assessment at screening is based on the LANO scorecard acc. to Le Rhun et al., 2019
Existing ability to undergo intrathecal therapy via an intraventricular catheter (e.g. Ommaya reservoir)
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.
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 Criteria15

Women during pregnancy and lactation.
Previous intrathecal nivolumab application.
Patient at "poor risk" (NCCN guidelines version 1.2021)
History of hypersensitivity to monoclonal antibodies
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
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
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
Patient with confirmed history of current autoimmune disease
Patients with any disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
Existence of clinically significant active infection (details see study protocol)
Inability to undergo MRI with contrast agent
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.
Existence of abnormal laboratory values for the following values in hematology, coagulation parameters, liver and renal function (details see study protocol)
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
Patients requiring chronic systemic corticosteroid therapy (> 10 mg prednisone or equivalent per day) or any other immunosuppressive therapies (including anti-TNF-a therapies)

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Interventions

DRUGNivolumab [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.