Description:
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.
Title
- Brief Title: Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection
- 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
Clinical Trial IDs
- ORG STUDY ID:
OS2966CED-001
- NCT ID:
NCT04608812
Conditions
- Glioma, Malignant
- High Grade Glioma
- Glioblastoma
- Glioblastoma Multiforme
- Anaplastic Astrocytoma
Interventions
Drug | Synonyms | Arms |
---|
OS2966 | | Direct Infusion of OS2966 |
Gadoteridol | | Direct Infusion of OS2966 |
Purpose
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.
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Direct Infusion of OS2966 | Experimental | OS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery using the Infuseon Cleveland Multiport Catheter | |
Eligibility Criteria
Inclusion Criteria
1. Male and female patients aged ≥ 18 years with histologically confirmed diagnosis of a
stereotactically accessible, supratentorial, contrast-enhancing WHO Grade III or IV
glioma (HGG) with a maximum volume between 2 and 6 cm3.
• NOTE: Only patients with a histologically confirmed diagnosis of WHO Grade IV glioma
(glioblastoma) meeting the above criteria will be eligible for enrollment in the first
3 dose cohorts (ie, dose concentration levels).
2. Patient must have completed standard of care chemoradiation (ie, treatment with
temozolomide and radiation) and have evidence of tumor recurrence or progression based
on imaging studies within the previous 21 days that supports a clinically-indicated
resection.
3. Patient understands the procedures and investigational nature of the study drug and
agrees to comply with study requirements by providing written informed consent.
4. Patient must have KPS ≥ 70.
5. At the time of study treatment, patients must have recovered from the toxic effects of
prior therapy or meet the following criteria, or both:
- More than 1 week from last noncytotoxic therapy
- More than 4 weeks from last cytotoxic therapy, radiation, or treatment with
bevacizumab
6. Patient must have adequate bone marrow and organ function as follows:
a. Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1500 μL
- Leukocyte count ≥ 3000 μL
- Hemoglobin ≥ 10 g/dL
- Platelet count ≥ 100,000 μL b. Adequate hepatic function:
- Aspartate aminotransferase (AST) < 2.5 × institutional upper limit of normal
(ULN)
- Alanine aminotransferase (ALT) < 2.5 × institutional ULN
- Total bilirubin ≤ 1.5 institutional ULN c. Adequate renal function:
- Glomerular filtration rate (GFR) ≥ 50 mL/min by Cockcroft Gault equation d.
Adequate coagulation function:
- Prothrombin time (PT)/partial thromboplastin time (PTT) not above institutional
norms. Note: patients receiving anticoagulant therapy are eligible for enrollment
but must have values below the ULN at the time of surgery.
7. Women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control) before study entry, for
the duration of the study, and for a minimum of 6 months after study completion.
8. Women of child-bearing potential must have a negative beta-human chorionic
gonadoptropin (hCG) serum pregnancy test within 21 days, and a negative urine
pregnancy test within 24 hours, before receiving study treatment.
9. Patients must be able to undergo contrast and noncontrast MRI studies.
Exclusion Criteria
A patient who meets any of the following criteria will be excluded from participation
in this study:
10. Patient has any significant medical illness that, in the investigator's opinion, may
compromise the patient's ability to participate in the study.
11. Patient has participated in another investigational therapeutic drug study in the
previous 4 weeks.
12. Patient has any of the following tumor characteristics:
- Multicentric disease - defined as tumors that have multiple discrete areas of
contrast enhancement separated by intervening brain and not connected by
T2-weighted-Fluid- attenuated Inversion Recovery (FLAIR) abnormality
- Contrast-enhancing tumor that extends into the opposite cerebral hemisphere
- Nonparenchymal tumor dissemination (subependymal or leptomeningeal)
- Tumor located in the posterior fossa
- Significant mass effect requiring urgent resection.
13. Patient has a history of hypersensitivity reaction to gadolinium contrast agents.
14. Patient is unable to undergo MRI.
15. Patient has a known history of human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS).
16. Patient has an active infection (requiring treatment) or an unexplained febrile
illness.
17. Patient is receiving anticoagulants, antiplatelets, or nonsteroidal anti-inflammatory
drugs (NSAIDs) that cannot be stopped for surgery.
18. Patient is receiving escalating doses of steroids to treat mass effect. Note: patients
on stable corticosteroid doses ≤ 4 mg of dexamethasone (or the equivalent of another
corticosteroid) daily are eligible for the study.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of qualifying treatment emergent adverse events or dose limiting toxicities |
Time Frame: | 28 days |
Safety Issue: | |
Description: | Estimated as described in the dosing protocols (accelerated titration and standard 3+3 dose-escalation design). |
Secondary Outcome Measures
Measure: | Spatial Distribution of OS2966 when delivered via the ICMC |
Time Frame: | Up to 48 hours pre-infusion and up to 24 hours post-infusion |
Safety Issue: | |
Description: | measured by comparing pre-infusion MR imaging to post-infusion MR Imaging |
Measure: | Tumor Response Rate |
Time Frame: | 12 months |
Safety Issue: | |
Description: | based upon MR imaging using RANO criteria assessed every 8 weeks after the initial safety follow up. |
Measure: | Time to Progression |
Time Frame: | Until progression of disease up to 12 months from infusion |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | OncoSynergy, Inc. |
Trial Keywords
- CED
- Convection-enhanced delivery
- recurrent glioblastoma
- recurrent high grade glioma
- immunotherapy
Last Updated
October 28, 2020