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. 2020 Aug 18;11(33):3105-3117.
doi: 10.18632/oncotarget.27684.

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 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 , Constantin Volovat  1   10
Affiliations

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 Volovat et al. Oncotarget. .

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/m2 NC-6004 on day one and 1,250 mg/m2 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.

Keywords: NC-6004; biliary tract cancer; bladder cancer; cisplatin; non-small cell lung cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST NanoCarrier provided research funding to all investigators: Simona Ruxandra Volovat MD, PhD, Tudor-Eliade Ciuleanu MD, Piotr Koralewski MD, Juneko E. Grilley Olson MD, Adina Croitoru MD, Krassimir Koynov MD, Stefano Stabile MD, Giulio Cerea MD and Constantin Volovat MD, PhD. Atsushi Osada and Iulian Bobe are employees of NanoCarrier. The authors have no other relevant conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Kaplan–Meier plot of progression-free survival in NSCLC patients.
Figure 2
Figure 2. Kaplan–Meier plot of progression-free survival in biliary tract cancer patients.
Figure 3
Figure 3. Kaplan–Meier plot of progression-free survival in bladder cancer patients stratified based on creatinine clearance and Eastern Cooperative Oncology Group performance status.
Figure 4
Figure 4. Kaplan–Meier plot of overall survival in NSCLC patients.
Figure 5
Figure 5. Kaplan–Meier plot of overall survival in biliary tract cancer patients.
Figure 6
Figure 6. Kaplan–Meier plot of overall survival in bladder cancer patients stratified based on creatinine clearance and Eastern Cooperative Oncology Group performance status.
Figure 7
Figure 7. Time profile of total platinum concentration for NC-6004 at 135 mg/m2.
Phase Ib data are shown as black circles and Phase II data as red circles.
Figure 8
Figure 8. Mean total platinum concentrations prior to the second gemcitabine infusion (168 h) in each cycle in patients with various tumor types.
Figure 9
Figure 9
(A) Total cisplatin exposure as indicated by Cmax after NC-6004 doses ranging from 10–180 mg/m2. (B) Total cisplatin exposure as indicated by AUC after NC-6004 doses ranging from 10–180 mg/m2.
See this image and copyright information in PMC

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