PMID- 33114652
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 11
DP  - 2020 Oct 26
TI  - Safety, Efficacy and Pharcacokinetics of Targeted Therapy with The Liposomal RNA 
      Interference Therapeutic Atu027 Combined with Gemcitabine in Patients with 
      Pancreatic Adenocarcinoma. A Randomized Phase Ib/IIa Study.
LID - 10.3390/cancers12113130 [doi]
LID - 3130
AB  - BACKGROUND: Atu027 is a liposomally formulated short interfering RNA with 
      anti-metastatic activity, which silences the expression of protein kinase N3 
      (PKN3) in the vascular endothelium. This trial was designed to assess the safety, 
      pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in 
      advanced pancreatic carcinoma (APC). METHODS: In total, 23 patients (pts) with 
      inoperable APC were randomly assigned to gemcitabine combined with two different 
      Atu027 schedules (0.235 mg/kg once weekly vs. 0.235 mg/kg twice weekly). 
      ClinicalTrials.gov Identifier: NCT01808638. RESULTS: The treatment was 
      well-tolerated. There were Grade 3 adverse events (AEs) in 9/11 pts (arm 1) and 
      11/12 pts (arm 2), while Grade 4 AEs were reported for two pts in each arm. The 
      AEs were mainly laboratory abnormalities without clinical significance. The 
      median progression-free survival reached statistical significance in patients who 
      had metastatic disease (1.6 vs. 2.9 months, p = 0.025). Disease control during 
      treatment was achieved in 4/11 pts (arm 1) and in 7/12 pts (arm 2). Pts in arm 1 
      experienced stable global health status while pts in arm 2 reported improvement. 
      CONCLUSIONS: Combining Atu027 with gemcitabine is safe and well tolerated. In pts 
      with metastatic APC, twice-weekly Atu027 is associated with significantly 
      improved outcomes. Our clinical results support the significant involvement of 
      the vascular endothelium in the spread of cancer, and thus the further 
      investigation of its target role.
FAU - Schultheis, Beate
AU  - Schultheis B
AD  - Department of Hematology and Oncology, Marien Hospital Herne, University of 
      Bochum, 44627 Herne, Germany.
FAU - Strumberg, Dirk
AU  - Strumberg D
AD  - Department of Hematology and Oncology, Marien Hospital Herne, University of 
      Bochum, 44627 Herne, Germany.
FAU - Kuhlmann, Jan
AU  - Kuhlmann J
AD  - Department of Medicine II, University Hospital Freiburg, 79106 Freiburg, Germany.
FAU - Wolf, Martin
AU  - Wolf M
AD  - Department of Medicine, Hospital Kassel, 34125 Kassel, Germany.
FAU - Link, Karin
AU  - Link K
AD  - Department of Medicine V, Hospital Nuernberg Nord, 90419 Nuernberg, Germany.
FAU - Seufferlein, Thomas
AU  - Seufferlein T
AD  - Department of Medicine I, Universitatsklinikum Ulm, 89081 Ulm, Germany.
FAU - Kaufmann, Joerg
AU  - Kaufmann J
AD  - Silence Therapeutics GmbH, 13125 Berlin, Germany.
FAU - Feist, Mathilde
AU  - Feist M
AD  - Department of Surgery, Charite-Universitatsmedizin Berlin, 13353 Berlin, Germany.
AD  - Medical faculty, Humboldt-Universitat zu Berlin, 10099 Berlin, Germany.
AD  - Berlin Institute of Health, 10178 Berlin, Germany.
FAU - Gebhardt, Frank
AU  - Gebhardt F
AD  - Silence Therapeutics GmbH, 13125 Berlin, Germany.
FAU - Khan, Mike
AU  - Khan M
AD  - Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
FAU - Stintzing, Sebastian
AU  - Stintzing S
AUID- ORCID: 0000-0002-3297-5801
AD  - Medical faculty, Humboldt-Universitat zu Berlin, 10099 Berlin, Germany.
AD  - Berlin Institute of Health, 10178 Berlin, Germany.
AD  - Department of Hematology, Oncology and Tumor Immunology, 
      Charite-Universitatsmedizin Berlin, 10117 Berlin, Germany.
FAU - Pelzer, Uwe
AU  - Pelzer U
AUID- ORCID: 0000-0001-9213-2737
AD  - Medical faculty, Humboldt-Universitat zu Berlin, 10099 Berlin, Germany.
AD  - Berlin Institute of Health, 10178 Berlin, Germany.
AD  - Department of Hematology, Oncology and Tumor Immunology, 
      Charite-Universitatsmedizin Berlin, 10117 Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01808638
PT  - Journal Article
DEP - 20201026
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7693593
OTO - NOTNLM
OT  - RNA interfering
OT  - pancreatic cancer
OT  - randomized trial
OT  - targeted therapy
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/10/30 06:00
MHDA- 2020/10/30 06:01
PMCR- 2020/10/26
CRDT- 2020/10/29 01:04
PHST- 2020/08/31 00:00 [received]
PHST- 2020/10/05 00:00 [revised]
PHST- 2020/10/18 00:00 [accepted]
PHST- 2020/10/29 01:04 [entrez]
PHST- 2020/10/30 06:00 [pubmed]
PHST- 2020/10/30 06:01 [medline]
PHST- 2020/10/26 00:00 [pmc-release]
AID - cancers12113130 [pii]
AID - cancers-12-03130 [pii]
AID - 10.3390/cancers12113130 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Oct 26;12(11):3130. doi: 10.3390/cancers12113130.