A Dose Escalation Study to Estimate MTD, DLTs and Pharmacokinetics After a Single Intracranial Dose of SI-053 as an add-on to the Current Standard of Care, in Adult Patients With Newly Diagnosed GBM (TARGLIO)
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|ClinicalTrials.gov Identifier: NCT04967690|
Recruitment Status : Not yet recruiting
First Posted : July 19, 2021
Last Update Posted : April 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Newly Diagnosed Glioblastoma Multiforme||Drug: SI-053||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Up to 27 subjects will be included in the trial (estimated; 21 subjects in total for dose escalation following a 3+3 rule based design for six doses in total, including three more subjects at RP2D, and an additional six subjects for dose expansion at RP2D).|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Dose Escalation Study to Estimate MTD, Identify DLTs and Study Pharmacokinetics Following a Single Dose of Intracranially Administered Temozolomide-based SI-053 as an add-on to the Current Standard of Care, in Adult Patients With Newly Diagnosed Glioblastoma|
|Estimated Study Start Date :||September 2022|
|Estimated Primary Completion Date :||March 2024|
|Estimated Study Completion Date :||May 2024|
Single arm study. Dose escalation will follow a rule-based 3 + 3 design using increasing doses of SI-053. Subjects will receive a single i.c. dose of room-tempered SI-053 gel, which will be applied onto the walls of the cavity formed after tumor resection using a sterile spatula.This will be followed by chemo-radiotherapy commencing at least 21 and no later than 35 days after SI-053 administration. The dose escalation part of the trial will follow a rule-based 3 + 3 design using a total of six dose levels of SI-053 (optional dose of 50 mg will be used to de-escalate in case of DLT at 75 mg) that consist of increasing amounts of TMZ in a constant amount of excipient and sterile WFI. These dose levels are planned to be tested in 21 subjects, including three more subjects at preliminary RP2D.The dose expansion phase will enroll an additional six subjects,to be treated at the RP2D in order to gather additional safety and preliminary efficacy data at that dose.
SI-053 will be used as an add-on to SoC for newly diagnosed GBM.In conjunction with surgical resection, SI-053 will be applied intracranially (i.c.) into the cavity that is formed after tumor resection. Post-operative chemoradiotherapy (including concomitant and adjuvant TMZ or following the CeTeG protocol) will be initiated at least 21 and no later than 35 days after SI-053 administration.
- Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) of a single i.c dose of SI-053 [ Time Frame: 6 months ]• Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) based on the occurrence of adverse events (AEs) reported according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
- SI-053 related adverse events (AEs) and toxicity [ Time Frame: 6 months ]SI-053 related AEs and toxicity determined by evaluation of the extent of edema (and associated use of steroids to control edema), neurological toxicities (e.g. sudden increase in seizure activity as a result of local inflammation), any infection (by requirement for antibiotic treatment), additional surgery or any additional treatment that would delay the chemoradiotherapy.
- Determination of plasma concentration of TMZ and its metabolite 5-amino-1H-imidazole-4-carboxamide (AIC) and PK parameters [ Time Frame: 6 months ]Determination of plasma concentration of TMZ and its metabolite 5-amino-1H-imidazole-4-carboxamide (AIC) and PK parameters
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): NCT04967690
|Contact: Breezy Lindqvist||0046 (0)email@example.com|
|Contact: Lili Li||0046 (0)firstname.lastname@example.org|
|Principal Investigator:||Manfred Westphal, Prof.Dr.Med.||Universitätklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany|