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JOURNAL ONKOLOGIE – STUDIE
IT-PD1

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

Rekrutierend

NCT-Nummer:
NCT05112549

Studienbeginn:
Oktober 2021

Letztes Update:
13.12.2023

Wirkstoff:
Nivolumab [Opdivo]

Indikation (Clinical Trials):
Meningeal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
University Hospital Tuebingen

Collaborator:
-

Studienleiter

Ghazaleh Tabatabai, Prof.Dr.
Study Director
University Hospital Tuebingen

Kontakt

Ghazaleh Tabatabai, Prof.Dr.
Kontakt:
Phone: +49 (0) 7071 - 2985018
E-Mail: ghazaleh.tabatabai@uni-tuebingen.de» Kontaktdaten anzeigen

Studienlocations
(3 von 9)

University Hospital Tübingen, Neurooncology
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ghazaleh Tabatabai, Prof. Dr.
Phone: 497071/29-83269
E-Mail: ghazaleh.tabatabai@uni-tuebingen.de» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

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)

Studien-Rationale

Primary outcome:

1. 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.



Secondary outcome:

1. 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.

Geprüfte Regime

  • 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.

Quelle: ClinicalTrials.gov


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