A phase I/II study of antroquinonol in combination with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer

Document Type

Conference Proceeding

Publication Date

1-22-2024

Publication Title

J Clin Oncol

Keywords

antroquinonol, gemcitabine, paclitaxel, adult, adverse drug reaction, aged, clinical article, conference abstract, drug dose escalation, female, gastrointestinal symptom, human, male, maximum tolerated dose, multiple cycle treatment, pancreas cancer, pancreas metastasis, phase 1 clinical trial, phase 2 clinical trial, side effect, special situation for pharmacovigilance

Abstract

Background: The survival of metastatic pancreatic cancer (mPC) is still disappointing though advancement in recent regimens. Antroquinonol, a new chemical entity, has been proposed for the treatment of neoplasms. In this phase I/II trial, we investigated the dose and efficacy of antroquinonol combined with gemcitabine and nab-paclitaxel (Gem/Nab-P) on mPC patients. Methods: Patients with chemo-naive, metastatic PDAC were enrolled. In the phase I, run-in drug-drug interaction (DDI) and dose escalation in a 3 + 3 designed to determine the maximal tolerated dose (MTD) of antroquinonol for phase II study. Gem/Nab-P (gemcitabine 1000 mg/ m2 and nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 weeks) was given from cycle 0 in phase I. The dose of antroquinonol was escalated from 200mg orally three times a day since the first cycle of Gem/Nab-P. The primary end points were median PFS and 6-month PFS rate. This trial is registered at ClinicalTrials.gov: NCT03310632. Results: In the phase I study of 15 patients, the MTD of antroquinonol was 300mg tid. In the phase II study of 40 patients, the median PFS was 5.3 (95% CI: 3.7-7.5) months and 6-month PFS rate was 40% (95% CI: 21%-57%), whereas median OS was 12.6 (95% CI: 8.8-15.8) months and12-month OS rate was 59.9% (95% CI: 37.8%-76.4%), respectively. The adverse events including hematological and non-hematological classes were decreased in the antroquinonol plus Gem/Nab-P, the GI discomforts were increased but manageable. Conclusions: In this phase I/II trial, antroquinonol plus Gem/Nab-P showed good efficacy in survival and less adverse events than a first-line strategy of Gem/Nab-P for mPC patients.

PubMed ID

Not assigned.

Volume

42

Issue

3

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