Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection
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|ClinicalTrials.gov Identifier: NCT04608812|
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : October 29, 2020
The primary goal of this Phase 1 study is to determine if a new investigational drug, OS2966, when delivered directly to the brain of adult participants with recurrent/progressive high-grade glioma (HGG) is safe and well tolerated.
OS2966 is a therapeutic antibody blocking a cell surface receptor governing fundamental biological processes that allow cancer cells to grow, spread and become resistant to cancer treatment. Despite availability of new promising cancer treatments, successful treatment of HGG has been limited by the presence of the brain's protective blood brain barrier (BBB). The BBB is made up of tightly knit cells that block entry of several substances including cancer treatments. To overcome this obstacle, a technique called convection-enhanced-delivery (CED) will be utilized to deliver OS2966 directly to the site of disease. Convection-enhanced delivery involves placement of one or more catheters into the brain tumor and tumor-infiltrated brain in order to slowly pump a therapy into the tissue. In this study, the Infuseon Cleveland Multiport Catheter (ICMC) will be used. The ICMC is a type of catheter developed specifically for direct delivery of therapies to the brain.
To be eligible for this study participants must require surgical resection of their recurrent HGG.
|Condition or disease||Intervention/treatment||Phase|
|Glioma, Malignant High Grade Glioma Glioblastoma Glioblastoma Multiforme Anaplastic Astrocytoma||Drug: OS2966 Drug: Gadoteridol Device: Infuseon Cleveland Multiport Catheter||Phase 1|
This study is an open-label, ascending-dose, 2-part study designed to determine the safety and tolerability of OS2966, as well as the optimal infusion parameters when administering OS2966 directly to the tumor and the surrounding tumor-infiltrated brain by CED in participants with recurrent/progressive HGG undergoing a surgical resection.
OS2966 is an anti-CD29 (Beta1 Integrin) monoclonal antibody (mAb) that has demonstrated preclinical efficacy in resistant/recurrent glioblastoma animal models. This study will recruit participants with recurrent/progressive high-grade glioma (HGG; WHO Grade III or IV glioma). The development of effective treatments for HGG has been limited by an infiltrative growth pattern, the blood brain barrier (BBB), and the rapid development of therapeutic resistance.
Convection-enhanced delivery is a specific technique that allows direct delivery of therapeutics to the brain and to brain tumors. Convection-enhanced delivery bypasses the BBB and allows for infusion of therapeutics that would otherwise be excluded from the central nervous system. Importantly, CEDs targeted delivery obviates systemic toxicity.
OS2966 will be delivered by CED using the Infuseon Cleveland Multiport Catheter (ICMC) in both parts of the study. The ICMC is a type of catheter developed specifically for direct delivery of therapies to the brain.
Participants enrolled in this study will undergo 2 staged parts of treatment. In Study Part 1, participants will receive a single intratumoral infusion of OS2966 directly to the contrast-enhancing bulk tumor by CED using one ICMC over 4 hours or until maximal tumor coverage is obtained. In Study Part 2, participants will undergo surgical resection of the previously infused tumor. Immediately following surgical resection, 2 ICMCs will be placed directly into the surrounding tumor-infiltrated brain, and OS2966 will be infused over a 4 hour period and then the catheters removed. To confirm the quality of OS2966 delivery, a gadolinium contrast agent will be added to OS2966 before each infusion in order to monitor the infusion via magnetic resonance imaging.
All participants will be closely monitored clinically, and through the use of imaging assessments to determine how effective OS2966 is at preventing further disease progression. Tumor tissue will be collected in both study parts to evaluate how well OS2966 binds to its intended target and to confirm mechanism of action. All enrolled patients will also receive standard supportive care therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Intratumorally and Intraparenchymally Administered OS2966 Using Convection-enhanced Delivery in Patients With Recurrent/Progressive High-grade Glioma Undergoing a Clinically-indicated Surgical Resection|
|Estimated Study Start Date :||October 2020|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||March 2022|
Experimental: Direct Infusion of OS2966
OS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery using the Infuseon Cleveland Multiport Catheter
OS2966 is a humanized monoclonal antibody antagonizing CD29 (Beta 1 integrin)
Gadoteridol is a contrast agent which will be added to OS2966 to allow investigators to observe how OS2966 distributes within the brain tumor. Gadoteridol is approved by the FDA for intravenous injection during an MRI scan. It is not approved by the FDA for administration directly into a tumor.
Device: Infuseon Cleveland Multiport Catheter
The Infuseon Cleveland Multiport Catheter is an FDA 510(k)-cleared device currently used in clinical studies to deliver therapeutics directly to brain tumors and the surrounding brain tssue.
- Number of qualifying treatment emergent adverse events or dose limiting toxicities [ Time Frame: 28 days ]
- Optimal Biological Dose [ Time Frame: 12 months ]Estimated as described in the dosing protocols (accelerated titration and standard 3+3 dose-escalation design).
- Spatial Distribution of OS2966 when delivered via the ICMC [ Time Frame: Up to 48 hours pre-infusion and up to 24 hours post-infusion ]measured by comparing pre-infusion MR imaging to post-infusion MR Imaging
- Tumor Response Rate [ Time Frame: 12 months ]based upon MR imaging using RANO criteria assessed every 8 weeks after the initial safety follow up.
- Time to Progression [ Time Frame: Until progression of disease up to 12 months from infusion ]
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): NCT04608812
|Contact: Anne-Marie Carbonell, MDemail@example.com|
|United States, Florida|
|Moffitt Cancer Center||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Emily Sparr 813-745-6350 firstname.lastname@example.org|
|Principal Investigator: Michael Vogelbaum, MD, PhD|