A multicenter, single-arm, basket design, phase II study of NC-6004 plus gemcitabine in patients with advanced unresectable lung, biliary tract, or bladder cancer
Simona Ruxandra Volovăț, Tudor–Eliade Ciuleanu, P. Koralewski, Juneko E. Grilley Olson, Adina Croitoru, Krassimir Koynov, Stefano Stabile, Giulio Cerea, Atsushi Osada, Iulian Bobe, Constantin Volovăț
Abstract
// Simona Ruxandra Volovat 1 , Tudor-Eliade Ciuleanu 2 , 3 , Piotr Koralewski 4 , Juneko E. Grilley Olson 5 , Adina Croitoru 6 , Krassimir Koynov 7 , Stefano Stabile 8 , Giulio Cerea 8 , Atsushi Osada 9 , Iulian Bobe 9 and Constantin Volovat 1 , 10 1 Department of Medicine III, Medical Oncology-Radiotherapy, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania 2 The Oncology Institue "Prof. Dr. Ion Chiricuta" Cluj-Napoca, Cluj-Napoca, Romania 3 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania 4 Ludwik Rydygier Memorial Specialist Hospital, Krakow, Poland 5 UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA 6 Department of Medical Oncology, Fundeni Clinical Institute, Bucharest, Romania 7 Multiprofile Hospital for Active Treatment Serdika, Sofia, Bulgaria 8 S C Oncologia Falck, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy 9 NanoCarrier Co., Ltd., Tokyo, Japan 10 Center of Oncology Euroclinic, Iasi, Romania Correspondence to: Constantin Volovat, email: [email protected] Keywords: cisplatin; NC-6004; non-small cell lung cancer; biliary tract cancer; bladder cancer Received: April 06, 2020     Accepted: July 07, 2020     Published: August 18, 2020 ABSTRACT NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patients. All patients received 135 mg/m 2 NC-6004 on day one and 1,250 mg/m 2 gemcitabine on days one and eight. The median progression-free survival was 3.9 months in NSCLC patients, 4.3 months in biliary tract cancer patients, and 6.8 months in bladder cancer patients fit for cisplatin treatment. The most frequently reported Grade 3 Treatment Emergent Adverse Events across all cohorts were nausea, anemia and neutropenia, and hyponatremia. Quality of life measures for patients who received the combined therapy were generally consistent with expectations for patients undergoing chemotherapy. Overall, combined NC-6004 and gemcitabine treatment resulted in long-lasting antitumor activity and had a favorable safety profile, suggesting that it should be investigated further as a therapy for various types of cancer.