A dose-escalation, Phase I study of a depot formulation of paclitaxel administered intralesionally in end-stage cancer patients with solid malignant tumors

Abstract

2131 Background: To determine the systemic plasma levels, safety and maximum tolerated dose (MTD) of a depot formulation of paclitaxel, OncoGel (paclitaxel/ReGel). This is a cremophor-free formulation which is liquid at administration temperature and rapidly forms a gel depot upon injection. The depot slowly degrades over several weeks allowing controlled release of paclitaxel within the tumor. Methods: A Phase I, dose-escalation study was conducted in 16 end-stage cancer patients with 18 superficially accessible solid malignant lesions at 6 investigative sites. Four paclitaxel dosages based on tumor volume were administered with 3 patients receiving 0.06 mg/cm3, 3 patients at 0.24 mg/cm3, 6 patients with 8 tumors at 0.48 mg/cm3, and 4 patients at 1.92 mg/cm3. There were 7 females and 9 males, ages 41 to 89, with treated tumors ranging from 0.7 cm3 to 19.0 cm3. The primary diagnoses included lymphoma, melanoma, lung, head and neck, laryngeal, thyroid, and breast cancer. Results: Blood samples were collected at predose, at 3, 6, 24 and 72 hours post-dose and then at weekly intervals for up to 9 weeks after injection in 13 subjects. Nine patients had no detectable paclitaxel and four patients had minimal, <2 ng/mL, levels in 5 of 153 plasma samples analyzed. Of the 103 reported adverse events (AEs), 12 mild or moderate AEs in eight patients were considered related to the drug. 9 of these AEs were pain or erythema at the injection site with the 3 others being bruising, drainage, and muscle spasm. No drug-related serious adverse events were reported in any patient. Although not a primary endpoint, analysis of tumor response showed size regression or stable disease in approximately 50% of the injected tumors. Conclusions: The Phase I study demonstrated the drug was well tolerated, maintained paclitaxel at the injection site, and suggested efficacy in stabilizing or reducing tumor growth. No MTD was reached. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MacroMed, Inc. MacroMed, Inc.