Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26) (IT-PD1)
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|ClinicalTrials.gov Identifier: NCT05112549|
Recruitment Status : Recruiting
First Posted : November 9, 2021
Last Update Posted : November 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Leptomeningeal Disease||Drug: Nivolumab [Opdivo]||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
This is a single arm phase 1 trial with two parts.
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
|Masking:||None (Open Label)|
|Official Title:||Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)|
|Actual Study Start Date :||October 12, 2021|
|Estimated Primary Completion Date :||September 30, 2025|
|Estimated Study Completion Date :||September 30, 2026|
Experimental: 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.
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.
- Assessment of Adverse Events for Dose Limiting Toxicities [Safety and Tolerabillity] [ Time Frame: up to 4 months after last dose ]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.
- Overall Survival [ Time Frame: last follow-up, up to 4 months after last dose ]The secondary endpoint is overall survival defined as the time interval from the date of first study administration to the date of progression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05112549
|Contact: Ghazaleh Tabatabai, Prof.Dr.||+49 (0) 7071 - firstname.lastname@example.org|
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|Contact: Ghazaleh Tabatabai, Prof. Dr. 497071/29-83269 email@example.com|
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|Ulm, Germany, 89081|
|Contact: Regine Mayer-Steinacker, Dr.|
|Study Director:||Ghazaleh Tabatabai, Prof.Dr.||University Hospital Tuebingen|