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

NCT04608812 | Terminated Phase 1 FDA Drug

• 1 other identifier: OS2966CED-001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Glioma, Malignant; High Grade Glioma; Glioblastoma; Glioblastoma Multiforme; Anaplastic Astrocytoma

Keywords

CED; Convection-enhanced delivery; recurrent glioblastoma; recurrent high grade glioma; immunotherapy

Outcome Measures

Primary Outcomes (2)

• Number of qualifying treatment emergent adverse events or dose limiting toxicities

  28 days

• Optimal Biological Dose

  Estimated as described in the dosing protocols (accelerated titration and standard 3+3 dose-escalation design).

  12 months

Secondary Outcomes (3)

• Spatial Distribution of OS2966 when delivered via CED

  Up to 48 hours pre-infusion and up to 24 hours post-infusion

• Tumor Response Rate

  12 months

• Time to Progression

  Until progression of disease up to 12 months from infusion

Study Arms (1)

Direct Infusion of OS2966

EXPERIMENTAL

OS2966 will be directly infused into the brain tumor and surrounding tumor infiltrated brain via convection-enhanced delivery

Drug: OS2966; Drug: Gadoteridol

Interventions

OS2966 DRUG

OS2966 is a humanized monoclonal antibody antagonizing CD29 (Beta 1 integrin)

Direct Infusion of OS2966

Gadoteridol DRUG

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.

Direct Infusion of OS2966

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:
• 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)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• OncoSynergy, Inc.: lead
• Infuseon Therapeutics, Inc.: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma

Interventions

gadoteridol

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 29, 2020
• Study Start: March 2, 2021
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

US (1)