Phase 1 single-center, dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma
| Autor: | Susan Boulton, John H. Sampson, Gordana Vlahovic, Allan H. Friedman, Vidyalakshmi Chandramohan, Katherine B. Peters, Stevie Threatt, James E. Herndon, Denise Lally-Goss, Eric S. Lipp, Dina Randazzo, Annick Desjardins, Patrick Healy, Darell D. Bigner |
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| Rok vydání: | 2017 |
| Předmět: |
Cancer Research
Adult patients business.industry medicine.drug_class Single Center medicine.disease Monoclonal antibody 03 medical and health sciences 0302 clinical medicine Oncology Immunotoxin 030220 oncology & carcinogenesis Glioma Immunology Cancer research Dose escalation Medicine Pseudomonas exotoxin Convection-Enhanced Delivery business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Oncology. 35:e13532-e13532 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.35.15_suppl.e13532 |
| Popis: | e13532 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin consisting of EGFR-wt and EGFRvIII monoclonal antibodies with a genetically engineered Pseudomonas exotoxin, PE-38KDEL. The primary objective is to determine the maximum tolerated dose of D2C7-IT when delivered intratumorally by convection enhanced delivery (CED). Methods: Inclusion criteria includes subjects with a single, recurrent supratentorial WHO grade III or IV glioma, KPS ≥ 70 and a washout of chemotherapy, bevacizumab or study drug of ≥ 4 weeks. Prior to administration of D2C7-IT, recurrent tumor must be confirmed by histopathology. A minimum of 2 subjects are accrued by dose level. Results: Currently, 23 subjects have been treated (16 male, 7 female) with a median age of 54 years. Out of 9 dose levels, 2 subjects have been treated at every dose except for 4 at dose level 3 (120 ng/ml) and 5 at dose 6 (405ng/ml). Adverse events possibly, probably or definitely related to D2C7-IT are mostly grade 1 or 2 events consisting of, but not limited to: intracranial hemorrhage (n = 1), stroke (n = 2), headache (n = 15), seizure (n = 5), confusion (n = 4), paresthesia (n = 4), dysarthria (n = 1), dysphasia (n = 4), visual disturbances (n = 7), fatigue (n = 4), gait disturbance (n = 2), elevated transaminases (n = 5), decreased platelets (n = 3), decreased neutrophil count (n = 1), nausea (n = 3), vomiting (n = 1), and thromboembolic event (n = 1). There was 1 dose limiting toxicity (grade 4 seizure at dose level 3), 2 grade 3 headaches and 1 grade 3 elevated ALT. 14 subjects are still alive with 6 remaining on study. So far, the longest survival time from infusion is 18.2+ months. Conclusions: D2C7-IT infusion via CED is safe with encouraging results. This dose escalation Phase I study is ongoing and will set the stage for the Phase II trial. Clinical trial information: NCT02303678. |
| Databáze: | OpenAIRE |
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