A phase I pharmacokinetic and safety study of Paclitaxel Injection Concentrate for Nano-dispersion (PICN) alone and in combination with carboplatin in patients with advanced solid malignancies and biliary tract cancers.

Abstract

PURPOSE:

Paclitaxel injection concentrate for nano-dispersion (PICN) is a Cremophor-free, nanotechnology-driven paclitaxel formulation. This phase I study examined the safety, tolerability, pharmacokinetics and maximum tolerated dose (MTD) of PICN alone and in combination with carboplatin. Its early efficacy in unresectable biliary tract cancers (BTCs) was also evaluated.

METHODS:

This multi-center study comprised two parts. Part A contained a dose-escalation cohort following "3 + 3" design using PICN monotherapy in advanced solid tumors (Part A1); Part A2 dose-expansion cohort was then conducted in advanced BTCs due to observed efficacy in Part A1. Part B1 and B2 evaluated escalating dose of PICN with carboplatin in advanced solid tumors. PICN was administered as a 30 min-infusion every 3 weeks without pre-medications for hypersensitivity reactions.

RESULTS:

Thirty-six patients received PICN monotherapy in Part A and 21 received PICN plus carboplatin in Part B. The MTD of PICN was determined to be 295 mg/m2 both as a monotherapy and in combination with carboplatin at AUC 5. Dose-proportional exposure in paclitaxel Cmax and AUC was observed overdose range from 175 to 325 mg/m2 for PICN monotherapy and its combination with carboplatin. Carboplatin did not alter PICN exposure. Clinically significant toxicities mainly include neutropenia and peripheral neuropathy. PICN monotherapy yielded a response rate of 20% in unresectable BTCs.

CONCLUSION:

This study demonstrated the safety and stable pharmacokinetics of PICN as a monotherapy and in combination with carboplatin. Single-agent PICN showed promising antitumor activity in advanced BTCs, warranting further studies to investigate its role in gastrointestinal cancers.

• Authors: Wen Wee Ma, Mojun Zhu, Elaine T Lam, Jennifer R Diamond, Grace K Dy, George A Fisher, Laura Williams Goff, Steven Alberts, Lynne A Bui, Akhil Sanghal, Mudgal Kothekar, Ajay Khopade, Geetanjali Chimote, Robert Faulkner, S Gail Eckhardt, Alex A Adjei, Antonio Jimeno
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 87 Issue 6 Pg. 779-788 (06 2021) ISSN: 1432-0843 [Electronic] Germany
• PMID: 33634324 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Biliary Tract Neoplasms (drug therapy)
• Carboplatin (adverse effects, pharmacokinetics, therapeutic use)
• Cohort Studies
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nanoparticles (administration & dosage)
• Paclitaxel (adverse effects, pharmacokinetics, therapeutic use)
• Treatment Outcome