Eintrag weiter verarbeiten
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma.
Gespeichert in:
| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Journal of Clinical Oncology, 34, 2016, 4_suppl, S. 385-385 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe |
|---|---|
| author |
Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe |
| spellingShingle |
Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe Journal of Clinical Oncology A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. Cancer Research Oncology |
| author_sort |
schultheis, beate |
| spelling |
Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2016.34.4_suppl.385 <jats:p> 385 </jats:p><jats:p> Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638. </jats:p> A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. Journal of Clinical Oncology |
| doi_str_mv |
10.1200/jco.2016.34.4_suppl.385 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTIwMC9qY28uMjAxNi4zNC40X3N1cHBsLjM4NQ |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTIwMC9qY28uMjAxNi4zNC40X3N1cHBsLjM4NQ |
| institution |
DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 |
| imprint |
American Society of Clinical Oncology (ASCO), 2016 |
| imprint_str_mv |
American Society of Clinical Oncology (ASCO), 2016 |
| issn |
1527-7755 0732-183X |
| issn_str_mv |
1527-7755 0732-183X |
| language |
English |
| mega_collection |
American Society of Clinical Oncology (ASCO) (CrossRef) |
| match_str |
schultheis2016aphaseibiiastudyofcombinationtherapywithgemcitabineandatu027inpatientswithlocallyadvancedormetastaticpancreaticadenocarcinoma |
| publishDateSort |
2016 |
| publisher |
American Society of Clinical Oncology (ASCO) |
| recordtype |
ai |
| record_format |
ai |
| series |
Journal of Clinical Oncology |
| source_id |
49 |
| title |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_unstemmed |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_full |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_fullStr |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_full_unstemmed |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_short |
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_sort |
a phase ib/iia study of combination therapy with gemcitabine and atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2016.34.4_suppl.385 |
| publishDate |
2016 |
| physical |
385-385 |
| description |
<jats:p> 385 </jats:p><jats:p> Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638. </jats:p> |
| container_issue |
4_suppl |
| container_start_page |
385 |
| container_title |
Journal of Clinical Oncology |
| container_volume |
34 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792347174731776001 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T17:51:03.853Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=A+phase+Ib%2FIIa+study+of+combination+therapy+with+gemcitabine+and+Atu027+in+patients+with+locally+advanced+or+metastatic+pancreatic+adenocarcinoma.&rft.date=2016-02-01&genre=article&issn=1527-7755&volume=34&issue=4_suppl&spage=385&epage=385&pages=385-385&jtitle=Journal+of+Clinical+Oncology&atitle=A+phase+Ib%2FIIa+study+of+combination+therapy+with+gemcitabine+and+Atu027+in+patients+with+locally+advanced+or+metastatic+pancreatic+adenocarcinoma.&aulast=Pelzer&aufirst=Uwe&rft_id=info%3Adoi%2F10.1200%2Fjco.2016.34.4_suppl.385&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792347174731776001 |
| author | Schultheis, Beate, Strumberg, Dirk, Kuhlmann, Jan, Wolf, Martin, Link, Karin, Seufferlein, Thomas, Kaufmann, Joerg, Gebhardt, Frank, Bruyniks, Nico, Pelzer, Uwe |
| author_facet | Schultheis, Beate, Strumberg, Dirk, Kuhlmann, Jan, Wolf, Martin, Link, Karin, Seufferlein, Thomas, Kaufmann, Joerg, Gebhardt, Frank, Bruyniks, Nico, Pelzer, Uwe, Schultheis, Beate, Strumberg, Dirk, Kuhlmann, Jan, Wolf, Martin, Link, Karin, Seufferlein, Thomas, Kaufmann, Joerg, Gebhardt, Frank, Bruyniks, Nico, Pelzer, Uwe |
| author_sort | schultheis, beate |
| container_issue | 4_suppl |
| container_start_page | 385 |
| container_title | Journal of Clinical Oncology |
| container_volume | 34 |
| description | <jats:p> 385 </jats:p><jats:p> Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638. </jats:p> |
| doi_str_mv | 10.1200/jco.2016.34.4_suppl.385 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTIwMC9qY28uMjAxNi4zNC40X3N1cHBsLjM4NQ |
| imprint | American Society of Clinical Oncology (ASCO), 2016 |
| imprint_str_mv | American Society of Clinical Oncology (ASCO), 2016 |
| institution | DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1 |
| issn | 1527-7755, 0732-183X |
| issn_str_mv | 1527-7755, 0732-183X |
| language | English |
| last_indexed | 2024-03-01T17:51:03.853Z |
| match_str | schultheis2016aphaseibiiastudyofcombinationtherapywithgemcitabineandatu027inpatientswithlocallyadvancedormetastaticpancreaticadenocarcinoma |
| mega_collection | American Society of Clinical Oncology (ASCO) (CrossRef) |
| physical | 385-385 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | American Society of Clinical Oncology (ASCO) |
| record_format | ai |
| recordtype | ai |
| series | Journal of Clinical Oncology |
| source_id | 49 |
| spelling | Schultheis, Beate Strumberg, Dirk Kuhlmann, Jan Wolf, Martin Link, Karin Seufferlein, Thomas Kaufmann, Joerg Gebhardt, Frank Bruyniks, Nico Pelzer, Uwe 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2016.34.4_suppl.385 <jats:p> 385 </jats:p><jats:p> Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638. </jats:p> A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. Journal of Clinical Oncology |
| spellingShingle | Schultheis, Beate, Strumberg, Dirk, Kuhlmann, Jan, Wolf, Martin, Link, Karin, Seufferlein, Thomas, Kaufmann, Joerg, Gebhardt, Frank, Bruyniks, Nico, Pelzer, Uwe, Journal of Clinical Oncology, A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma., Cancer Research, Oncology |
| title | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_full | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_fullStr | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_full_unstemmed | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_short | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_sort | a phase ib/iia study of combination therapy with gemcitabine and atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| title_unstemmed | A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma. |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2016.34.4_suppl.385 |