A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer.

Abstract

BACKGROUND:

PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer.

METHODS:

Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)).

RESULTS:

A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively.

CONCLUSION:

PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.

• Authors: A H Ko, M A Tempero, Y-S Shan, W-C Su, Y-L Lin, E Dito, A Ong, Y-W Wang, C G Yeh, L-T Chen
• Journal: British journal of cancer (Br J Cancer) Vol. 109 Issue 4 Pg. 920-5 (Aug 20 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23880820 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Combinations
• Liposomes
• Sucrose
• Irinotecan
• irinotecan sucrosofate
• Camptothecin

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Camptothecin (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Drug Combinations
• Female
• Humans
• Irinotecan
• Liposomes
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Salvage Therapy
• Sucrose (analogs & derivatives, therapeutic use)
• Treatment Outcome