Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Brain Neoplasms

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

D2C7-(scdsFv)-PE38KDEL

Immunotoxins

Immunoconjugates

Immunologic Factors

Recurrent malignant glioma patients will receive D2C7-IT, delivered intratumorally by CED following confirmatory diagnostic biopsy.

D2C7-IT is a single-chain fragment variable (scFv) monoclonal antibody (Mab) fragment immunotoxin with high binding affinity for both EGFRwt- and EGFRvIII-expressing glioblastoma multiforme (GBM) cells.

D2C7-IT

Dan Landi, MD

This is a Phase I study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of D2C7-IT (D2C7 Immunotoxin) when delivered intratumorally by convection-enhanced delivery (CED) to recurrent World Health Organization (WHO) grade III and IV malignant glioma patients, and/or to determine what dose will be considered in a Phase II trial. Patients with recurrent WHO grade III and IV malignant glioma who meet eligibility criteria will be enrolled into the study. Immediately following the stereotactically-guided tumor biopsy conducted as standard of care, up to three additional core biopsies will be obtained for molecular genetic testing. After these biopsies are obtained, subjects will have up to 2 catheters inserted. If the biopsy indicates a proven diagnosis of recurrent malignant glioma (diagnosis results are typically received within 24-48 hours following biopsy), the investigators will proceed with the D2C7-IT infusion. If no tumor is identified, the catheters will be removed. A continuous intratumoral infusion of D2C7-IT will be administered over 72 hours while in the hospital.

This is a Phase I study to determine the maximum tolerated dose (MTD) of D2C7-IT, when delivered intratumorally by convection-enhanced delivery (CED) following confirmatory diagnostic biopsy in recurrent World Health Organization (WHO) grade III and IV malignant glioma patients, and/or to determine what dose will be considered in a phase II trial. The patient will remain in the hospital during the entire infusion. At the completion of the infusion, the catheters will be removed within 6 hours and a CT scan will be obtained after the catheters are pulled. The patient will be observed in hospital for a minimum of another 6 hours.

A two-stage continual reassessment method (CRM) design will be used to determine the MTD of D2C7-IT where the first stage involves dose escalation in successive patients until an initial dose-limiting toxicity (DLT) is observed. Cohorts of 2 patients will be accrued to this study within both stages of the trial. The first patient of each cohort will be observed through the completion of the D2C7-IT infusion, before additional patients in that cohort are treated. Once the optimal dose level of D2C7-IT is determined (dose escalation completed), a total of 27 recurrent patients with WHO grade IV malignant glioma patients will be treated at that dose level as a dose expansion cohort.

Following D2C7-IT infusion, subjects will be evaluated in clinic at 2 weeks for adverse events and followed at 4 and 8 weeks and every 8 weeks thereafter until 48 weeks.

D2C7 for Adult Patients With Recurrent Malignant Glioma

Phase I Single-Center, Dose Escalation Study of D2C7-IT Administered Intratumorally Via Convection-Enhanced Delivery for Adult Patients With Recurrent Malignant Glioma

The MTD is the dose that results in an estimated DLT rate based upon the CRM model that is nearest to the target DLT rate of 0.25. DLTs include any ≥ Gr.3 non-hematologic toxicities, any ≥ Gr.3 neurological toxicities, and any ≥ Gr.3 hematologic toxicities that do not resolve to pre-treatment baseline or ≤ Gr.1 within 2 weeks or any toxicity that resolves within the 2 week period, but then recurs during that same 2 week period. Adverse events will be collected using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

OS is defined at the time between administration of D2C7-IT and death. For patients alive, OS will be censored at the time of last follow-up. Kaplan-Meier methods will be used to estimate median OS and PFS.

Cox proportional hazards models will explore the relationship between EGFRvIII and EGFRwt expression as measured by immunohistochemistry (IHC), polymerase chain reactions (PCR), and fluorescence in situ hybridization (FISH) and PFS and OS.

Darell Bigner

Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor

Glioblastoma

Antineoplastic Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Single PVSRIPO infusion at a dose of 5x10\^7 tissue culture infected dose (TCID50). Atezolizumab infusions at a dose of 1200 mg every three weeks for up to two years.

PVSRIPO

Darell D Bigner, MD, PhD

Dina M Randazzo, DO

This study evaluates the safety of PVSRIPO treatment in combination with Atezolizumab in patients with WHO grade IV malignant glioma. All patients will receive a single PVSRIPO infusion followed by atezolizumab infusions every three weeks for up to two years.

The purpose of this phase1b/2 study of atezolizumab in combination with oncolytic polio/rhinovirus recombinant (PVSRIPO) in patients with recurrent World Health Organization (WHO) grade IV malignant glioma is to assess the safety of the combination of PVSRIPO + atezolizumab, as well as describe the survival of patients receiving this novel therapy combination. Patients will receive an intratumoral infusion of PVSRIPO followed by atezolizumab treatment with possible surgical resection after the first atezolizumab treatment at the discretion of the treating neurosurgeon.

Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma

A Phase 1b/2 Trial of PVSRIPO in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma

Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, or any life-threatening event, or treatment-related death.

Proportion of patients alive at 24 months after PVSRIPO infusion

Istari Oncology, Inc.

Genentech, Inc.

Sponsor-Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
D2C7 for Adult Patients With Recurrent Malignant Glioma	NCT02303678	Malignant Gliom... Brain Tumor, Re...	D2C7-IT	18 Years -	Duke University
Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma	NCT03973879	Malignant Gliom...	PVSRIPO Atezolizumab	18 Years -	Duke University

Spots Global Cancer Trial Database for bigner

Every month we try and update this database with for bigner cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bigner

Every month we try and update this database with for bigner cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bigner cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.