Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer

Abstract

OncoGel, a novel injectable formulation of paclitaxel in a biocompatible biodegradable gel (ReGel), provides controlled release of paclitaxel at the injection site, resulting in high intralesional paclitaxel concentrations and continuous radiosensitization without attendant systemic toxicities. This dose-escalation study evaluated the toxicity, pharmacokinetics, and preliminary antitumor activity of OncoGel injected intralesionally in patients with inoperable esophageal cancer who were candidates for palliative external-beam radiotherapy (RT). Eleven patients with inoperable advanced esophageal cancer received a single administration of OncoGel into the primary tumor using conventional endoscopic techniques. Three cohorts received approximately one-third of the tumor volume with increasing paclitaxel concentrations to achieve 0.48, 1.0, and 2.0 mg paclitaxel/cm tumor volume. Subsequent to injection, RT was initiated (50.4 Gy in 1.8 Gy fractions). Pharmacokinetic sampling was performed. All patients completed the study. No dose-limiting toxicities were reported. Dysphagia improved and tumor size decreased in most patients. Biopsies were negative for carcinoma in 4 of 11 patients. Peak paclitaxel plasma concentrations were low (0.53-2.73 ng/ml) and directly related to the absolute amount of paclitaxel administered. Paclitaxel was detectable in plasma for 24 h in all patients and for 3 weeks in six patients. OncoGel given as an adjunct to RT was well tolerated in patients with inoperable esophageal cancer and provided prolonged paclitaxel release with minimal systemic exposure. OncoGel plus RT seemed to reduce tumor burden as evidenced by dysphagia improvement, tumor size reduction, and negative esophageal biopsies. The addition of OncoGel to combined modality therapy merits continued clinical development.

PEG- b -PLA micelles and PLGA- b -PEG- b -PLGA sol–gels for drug delivery

“…Oncogel ™ entered phase 2 clinical trials for the treatment of esophageal cancer based relative ease of access to tumors by endoscopic ultrasound-guided injection and visualization and potential for synergy in combination with radiation treatment [62, 65]. Oncogel ™ was provided as ready-to-use single use prefilled glass syringes, stored at −20 °C and thawed at room temperature for 1 hour prior to injection.…”

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

“…We also note that while being less invasive compared to F98-based models, orthotopic models established with 9L GS have been widely used in the preclinical setting to determine the potential of novel therapeutic approaches to be tested in clinical trials [43,44]. Indeed, clinical trials for Gliadel ® [45–47] and OncoGel™ [48–50] were initiated based on pre-clinical evaluation in the 9L GS model.…”

Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

“…The term ‘bioactive factor’ refers to small-molecule drugs like anticancer drugs [7,8], genetic agents [9–11] and proteins such as growth factors (GFs) [2,12], which have been used to treat human diseases, guide and direct cell functions and/or enhance tissue regeneration. Hydrogels, highly-hydrated three-dimensional networks of crosslinked hydrophilic polymer, hold great potential in pharmaceutical and biomedical applications [4,13–18].…”