D2C7 for Adult Patients With Recurrent Malignant Glioma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02303678|
Recruitment Status : Recruiting
First Posted : December 1, 2014
Last Update Posted : May 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Malignant Glioma Brain Tumor, Recurrent||Drug: D2C7-IT||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Single-Center, Dose Escalation Study of D2C7-IT Administered Intratumorally Via Convection-Enhanced Delivery for Adult Patients With Recurrent Malignant Glioma|
|Actual Study Start Date :||May 5, 2015|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2020|
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.
- Maximum tolerated dose (MTD) and/or recommended phase II dose of D2C7-IT [ Time Frame: 2 weeks after D2C7 administration ]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.
- Overall survival (OS) [ Time Frame: 3 years ]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.
- Association between EGFRvIII and EGFRwt expression and PFS and OS. [ Time Frame: 3 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02303678
|Contact: Dina Randazzo, DOemail@example.com|
|Contact: Susannah Kromfirstname.lastname@example.org|
|United States, North Carolina|
|Preston Robert Tisch Brain Tumor Center at Duke||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Susannah Krom 919-684-5301 email@example.com|
|Contact: Stevie Threatt 919-684-5301 firstname.lastname@example.org|
|Principal Investigator:||Dina Randazzo, DO||Preston Robert Tisch Brain Tumor Center at Duke University Medical Center|