Glioma, MalignantPhase 1NCT04608812
Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection
A Phase 1 study testing OS2966 and Gadoteridol in people with Glioma, Malignant and High Grade Glioma, run by OncoSynergy, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Malignant, High Grade Glioma, Glioblastoma
- What is being tested?
- OS2966 and Gadoteridol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2021to 27 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 20 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).
- 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.
- Patient understands the procedures and investigational nature of the study drug and agrees to comply with study requirements by providing written informed consent.
- Patient must have KPS ≥ 70.
- At the time of study treatment, patients must have recovered from the toxic effects of prior therapy or meet the following criteria, or both:
Show all 22Show fewer
- More than 1 week from last noncytotoxic therapy
- More than 4 weeks from last cytotoxic therapy, radiation, or treatment with bevacizumab
- Patient must have adequate bone marrow and organ function as follows:
- 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.
- 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.
- 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.
- Patients must be able to undergo contrast and noncontrast MRI studies.
Who cannot join
- A patient who meets any of the following criteria will be excluded from participation in this study:
- Patient has any significant medical illness that, in the investigator's opinion, may compromise the patient's ability to participate in the study.
- Patient has participated in another investigational therapeutic drug study in the previous 4 weeks.
- 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
Show all 15Show fewer
- Nonparenchymal tumor dissemination (subependymal or leptomeningeal)
- Tumor located in the posterior fossa
- Significant mass effect requiring urgent resection.
- Patient has a history of hypersensitivity reaction to gadolinium contrast agents.
- Patient is unable to undergo MRI.
- Patient has a known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
- Patient has an active infection (requiring treatment) or an unexplained febrile illness.
- Patient is receiving anticoagulants, antiplatelets, or nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be stopped for surgery.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
To be eligible for this study participants must require surgical resection of their recurrent HGG.
Read the 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.
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 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, catheters 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.
- Conditions
- Glioma, Malignant, High Grade Glioma, Glioblastoma, Glioblastoma Multiforme, Anaplastic Astrocytoma
- Being tested
- OS2966, Gadoteridol
- Keywords
- CED, Convection-enhanced delivery, recurrent glioblastoma, recurrent high grade glioma, immunotherapy
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OS2966Drug
OS2966 is a humanized monoclonal antibody antagonizing CD29 (Beta 1 integrin)
GadoteridolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Direct Infusion of OS2966 | Experimental | OS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery Receives: Drug: OS2966; Drug: Gadoteridol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of qualifying treatment emergent adverse events or dose limiting toxicities
Measured: 28 days
Optimal Biological Dose
Estimated as described in the dosing protocols (accelerated titration and standard 3+3 dose-escalation design).
Measured: 12 months
Secondary outcomes (3)
Spatial Distribution of OS2966 when delivered via CED
measured by comparing pre-infusion MR imaging to post-infusion MR Imaging
Measured: Up to 48 hours pre-infusion and up to 24 hours post-infusion
Tumor Response Rate
based upon MR imaging using RANO criteria assessed every 8 weeks after the initial safety follow up.
Measured: 12 months
Time to Progression
Measured: Until progression of disease up to 12 months from infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start2 Mar 2021
- Primary completion27 Feb 2023
- Study completion27 Feb 2023
Why it stopped: Slow enrollment and financial constraints.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioma, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- OncoSynergy, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Infuseon Therapeutics, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04608812
- Sponsor's protocol ID
- OS2966CED-001
- Status last verified
- Aug 2023
- First submitted
- 21 Oct 2020
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04608812
- Acronym / sponsor ID
- OS2966CED-001
- Conditions
- Glioma, Malignant, High Grade Glioma, Glioblastoma, Glioblastoma Multiforme, Anaplastic Astrocytoma
- Keywords
- CED, Convection-enhanced delivery, recurrent glioblastoma, recurrent high grade glioma, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment and financial constraints.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- OncoSynergy, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Infuseon Therapeutics, Inc.
- Study start
- 2 Mar 2021 (actual)
- Primary completion
- 27 Feb 2023 (actual)
- Study completion
- 27 Feb 2023 (actual)
- First posted
- 29 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
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 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, catheters 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Direct Infusion of OS2966 | Experimental | Drug: OS2966, Drug: GadoteridolOS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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 20 cm3.
- 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.
- Patient understands the procedures and investigational nature of the study drug and agrees to comply with study requirements by providing written informed consent.
- Patient must have KPS ≥ 70.
- At the time of study treatment, patients must have recovered from the toxic effects of prior therapy or meet the following criteria, or both:
Key exclusion criteria (15 listed)
- A patient who meets any of the following criteria will be excluded from participation in this study:
- Patient has any significant medical illness that, in the investigator's opinion, may compromise the patient's ability to participate in the study.
- Patient has participated in another investigational therapeutic drug study in the previous 4 weeks.
- Patient has any of the following tumor characteristics:
- Patient has a history of hypersensitivity reaction to gadolinium contrast agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OS2966OS2966 is a humanized monoclonal antibody antagonizing CD29 (Beta 1 integrin) | Drug | Direct Infusion of OS2966 |
| GadoteridolGadoteridol 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. | Drug | Direct Infusion of OS2966 |
Primary outcome
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).
3 secondary outcomes
Spatial Distribution of OS2966 when delivered via CED
Time frame: Up to 48 hours pre-infusion and up to 24 hours post-infusion
Tumor Response Rate
Time frame: 12 months
Time to Progression
Time frame: Until progression of disease up to 12 months from infusion
Results and safety
The study was stopped early (reason given: Slow enrollment and financial constraints.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
Related trials for Glioma, Malignant
RecruitingPhase 1
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
RecruitingEarly Phase 1
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Diffuse Glioma, Malignant Glioma
Active, not recruitingPhase 1
Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
Recurrent Glioblastoma, Recurrent Malignant Glioma
Active, not recruitingPhase 1/2
A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
Malignant Glioma
RecruitingPhase 2
Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
High Grade Glioma, CNS Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OS2966 and Gadoteridol in people with Glioma, Malignant and High Grade Glioma, run by OncoSynergy, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrollment and financial constraints.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of qualifying treatment emergent adverse events or dose limiting toxicities (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.