A49: Phase I Trial of Intraperitoneal Paclitaxel-loaded TPM for Treatment of Peritoneal Carcinomatosis

Peritoneal carcinomatosis is a common and deadly metastatic spread from many cancer types. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for only a small subset of patients. Development of novel regional therapeutic strategy is critically needed.



Methods: Paclitaxel-loaded tumor-penetrating microparticles (TPM) are cGMP-grade multi-component, biocompatible, biodegradable, polymeric paclitaxel-loaded microparticles designed to be retained in peritoneal cavity, adhere to peritoneal tumors, penetrate the inner tumor layers, and deliver controlled and effective drug levels. Extensive pharmacokinetics (PK) and pharmacodynamics (PD) studies were conducted in preclinical mouse models.


Results: Design and production of TPM is sponsored by NIH-NCATS under grant number X01TR000329. Preclinical data in mouse models with peritoneal carcinomatosis showed promising drug penetration into bulky peritoneal tumors with sustained drug release. We have now designed a Phase 1 first-in-human dose-escalation trial with intraperitoneal infusion of TPM for treating patients with unresectable peritoneal carcinomatosis. We have obtained an IND from the FDA and IRB approval for this trial. Patient enrollment is anticipated starting in December 2021. Extensive pharmacokinetic and pharmacodynamic study along with quantitative computational modeling will be conducted for adopting a Model-Informed Drug Development (MIDD) process.


Conclusions: TPM is a promising drug delivery platform for treating unresectable peritoneal carcinomatosis. At the conclusion of this trial, recommended Phase 2 dose will be determined. Expansion to multicenter Phase 2 trial is highly anticipated.