Clinical Trials /

Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection

NCT04608812

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.

Related Conditions:
  • Malignant Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
OS2966Direct Infusion of OS2966
GadoteridolDirect 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

NameTypeDescriptionInterventions
Direct Infusion of OS2966ExperimentalOS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery using the Infuseon Cleveland Multiport Catheter
  • OS2966
  • Gadoteridol

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