Background: Nanoparticles have been studied in association with chemotherapy, with objective of increasing the concentration of the drug in neoplastic cells and, thus, increasing its antitumor action. Nab-paclitaxel is a well-known nanotechnology association between paclitaxel and albumin and can be used in the treatment of advanced pancreatic cancer. LDE-Paclitaxel is a combination of paclitaxel and a synthetic molecule of low-density lipoprotein (LDE). It was previously evaluated in patients with gynaecological malignancies undergoing third-line treatment and showed higher rates of disease control than conventional regimens described in the literature. Our objective was to evaluate the efficacy of LDE-paclitaxel in the treatment of advanced pancreatic cancer (stage III and IV) in second or third line of therapy. Methods: This was a prospective phase I/II, single-arm study, in which we delivered LDE-Paclitaxel at a weekly dose of 85mg/m² to patients with pancreatic adenocarcinoma in second or third-line. The patients must had been through treatment of at least one standard chemotherapy scheme. Results: From October 2020 to November 2021, nine patients with advanced pancreatic adenocarcinoma were enrolled in this prospective, single-arm, phase 1/2 study in which we offered LDE-Paclitaxel at a dose of 85mg/m² intravenously, after progression to gemcitabine. During this period, patients underwent a maximum of 5 cycles, with no need to reduce the medication dose in any of the cycles, for any of the patients. LDE-paclitaxel presented mostly grade 1 and 2 toxicities, mainly anaemia and neuropathy; Grade 3 toxicity was presented by only 1 patient, which was acute kidney injury. Median overall patient survival was 20.14 months, and patient survival after enrolment in the study and initiation of LDE-paclitaxel use was close to 5 months, with no decline in the assessed quality of life indices. Conclusions: LDE-paclitaxel appears to be more tolerable, viable and less toxic than other standard chemotherapy in this setting. Our results suggest that LDE-paclitaxel could be a therapeutic possibility for patients with metastatic pancreatic cancer. For a better evaluation, further studies would be necessary, to obtain more data on the use of this medication in clinical practice and for a better understanding of other important outcomes. Clinical trial information: 4237198.