First-line treatment of inoperable pancreatic adenocarcinoma with lipid complexed paclitaxel nanoparticles plus gemcitabine compared with gemcitabine monotherapy. A prospective RCT - phase II study

Abstract

4618 Background: Cationic lipid complexed paclitaxel (EndoTAG-1[E]) is a novel therapy destroying tumor blood vessels. E targets activated endothelial cells due to its cationic carrier liposomes binding preferentially to negatively charged cells of tumor vessels. Methods: CT4001 is an open-label phase II RCT of 1st line combination treatment with weekly gemcitabine (G) (arm 1: G mono 1,000 mg/m²) and twice weekly E at 3 different dose levels (arm 2/3/4: G+E 11/22/44 mg/m²) in patients with inoperable pancreatic adenocarcinoma (PC). Treatment was at least 7 weeks with the option to continue in case of clinical benefit (SD or better), and follow-up for survival. Results: 100 patients from a planned interim analysis. According to TNM at screening, 80% had metastatic disease and 20% had locally advanced disease. Median sum of longest target lesion diameter (RECIST) at screening was 55 mm in arm 1, 93 mm in arm 2, 74 mm in arm 3, and 63 mm in arm 4. Patients were ECOG grade 0 (39%), 1 (52%) or 2 (9%) with slightly more patients with ECOG grade 2 in the E arms (4% in arm 1, 8% in arm 2, 13% in arm 3, 13% in arm 4). Serious treatment adverse events were in 7 patients (29%) in arm 1, 9 patients (36%) in arm 2, 10 patients (42%) in arm 3, and 11 (48%) patients in arm 4. The most frequent AEs attributable to E treatment were pyrexia and chills. The addition of E to G did not lead to elevated bone marrow toxicity. Blood and lymphatic system disorders were reported in 58% of arm 1, 52% of arm 2, 54% of arm 3, and 65% of arm 4. Neutropenia was 50% in arm 1, 24% in arm 2, 17% in arm 3, and 52% in arm 4. No death was related to study medication. Tumor response at end of treatment according to RECIST: PR was 21% in arm 1, 14% in arm 2, 12% in arm 3, 29% in arm 4. SD was 48% in arm 2 and 53% in arm 3 higher than 26% in arm 1 and 14% in arm 4. Pain and EORTC PAN-26 QoL assessments were initially lower in arm 1, suggestive of less tumor burden in arm 1. In all 4 arms, pain and PAN-26 QoL improved for the duration of the study. Conclusions: As in the phase I studies, E has a favourable safety profile. Addition of E to G monotherapy is well tolerated and may add clinical benefit to patients with advanced PC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medigene AG