Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial

Gayle S. Jameson, Erkut Borazanci, Hani M. Babiker, Elizabeth Poplin, Anna A. Niewiarowska, Michael S. Gordon, Michael T. Barrett, Adam Rosenthal, Amy Stoll-D'astice, John Crowley, Lynn Shemanski, Ron L. Korn, Karen Ansaldo, Leticia Lebron, Ramesh K. Ramanathan, Daniel D. Von Hoff

Research output: Contribution to journalArticle

Abstract

Importance: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. Objective: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). Design, Setting, and Participants: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. Interventions: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m2, 37.5 mg/m2, and 50 mg/m2, on days 1 and 8 of a 21-day cycle. Main Outcomes and Measures: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). Results: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m2. The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%. Conclusions and Relevance: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers.

Original languageEnglish (US)
JournalJAMA Oncology
DOIs
StateAccepted/In press - Jan 1 2019

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gemcitabine
Pancreatic Neoplasms
Cisplatin
Clinical Trials
Therapeutics
Adenocarcinoma
Albumin-Bound Paclitaxel
Platinum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer : A Phase 1b/2 Pilot Clinical Trial. / Jameson, Gayle S.; Borazanci, Erkut; Babiker, Hani M.; Poplin, Elizabeth; Niewiarowska, Anna A.; Gordon, Michael S.; Barrett, Michael T.; Rosenthal, Adam; Stoll-D'astice, Amy; Crowley, John; Shemanski, Lynn; Korn, Ron L.; Ansaldo, Karen; Lebron, Leticia; Ramanathan, Ramesh K.; Von Hoff, Daniel D.

In: JAMA Oncology, 01.01.2019.

Research output: Contribution to journalArticle

Jameson, GS, Borazanci, E, Babiker, HM, Poplin, E, Niewiarowska, AA, Gordon, MS, Barrett, MT, Rosenthal, A, Stoll-D'astice, A, Crowley, J, Shemanski, L, Korn, RL, Ansaldo, K, Lebron, L, Ramanathan, RK & Von Hoff, DD 2019, 'Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial', JAMA Oncology. https://doi.org/10.1001/jamaoncol.2019.3394
Jameson, Gayle S. ; Borazanci, Erkut ; Babiker, Hani M. ; Poplin, Elizabeth ; Niewiarowska, Anna A. ; Gordon, Michael S. ; Barrett, Michael T. ; Rosenthal, Adam ; Stoll-D'astice, Amy ; Crowley, John ; Shemanski, Lynn ; Korn, Ron L. ; Ansaldo, Karen ; Lebron, Leticia ; Ramanathan, Ramesh K. ; Von Hoff, Daniel D. / Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer : A Phase 1b/2 Pilot Clinical Trial. In: JAMA Oncology. 2019.
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title = "Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial",
abstract = "Importance: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. Objective: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). Design, Setting, and Participants: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. Interventions: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m2, 37.5 mg/m2, and 50 mg/m2, on days 1 and 8 of a 21-day cycle. Main Outcomes and Measures: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). Results: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56{\%}) were men, and most (24) were white (96{\%}). The maximum tolerable dose of cisplatin was 25 mg/m2. The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68{\%}]), anemia (8 patients [32{\%}]), and neutropenia (6 patients [24{\%}]). Fatal events occurred for 3 patients (12{\%}); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8{\%}), which was below the primary end point of 25{\%}, 15 partial responses (62{\%}), 4 stable disease (17{\%}), and 3 progressive disease (12{\%}), with median overall survival of 16.4 (95{\%} CI, 10.2-25.3) months; 16 patients (64{\%}) were alive at 1 year, 10 (40{\%}) at 2 years, 4 (16{\%}) at 3 years, and 1 (4{\%}) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95{\%} CI, 6.0-12.5) months. Thus, the overall response rate was 71{\%}, and the disease control rate was 88{\%}. Conclusions and Relevance: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers.",
author = "Jameson, {Gayle S.} and Erkut Borazanci and Babiker, {Hani M.} and Elizabeth Poplin and Niewiarowska, {Anna A.} and Gordon, {Michael S.} and Barrett, {Michael T.} and Adam Rosenthal and Amy Stoll-D'astice and John Crowley and Lynn Shemanski and Korn, {Ron L.} and Karen Ansaldo and Leticia Lebron and Ramanathan, {Ramesh K.} and {Von Hoff}, {Daniel D.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamaoncol.2019.3394",
language = "English (US)",
journal = "JAMA oncology",
issn = "2374-2437",
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TY - JOUR

T1 - Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment among Patients with Advanced Pancreatic Cancer

T2 - A Phase 1b/2 Pilot Clinical Trial

AU - Jameson, Gayle S.

AU - Borazanci, Erkut

AU - Babiker, Hani M.

AU - Poplin, Elizabeth

AU - Niewiarowska, Anna A.

AU - Gordon, Michael S.

AU - Barrett, Michael T.

AU - Rosenthal, Adam

AU - Stoll-D'astice, Amy

AU - Crowley, John

AU - Shemanski, Lynn

AU - Korn, Ron L.

AU - Ansaldo, Karen

AU - Lebron, Leticia

AU - Ramanathan, Ramesh K.

AU - Von Hoff, Daniel D.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Importance: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. Objective: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). Design, Setting, and Participants: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. Interventions: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m2, 37.5 mg/m2, and 50 mg/m2, on days 1 and 8 of a 21-day cycle. Main Outcomes and Measures: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). Results: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m2. The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%. Conclusions and Relevance: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers.

AB - Importance: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. Objective: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). Design, Setting, and Participants: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. Interventions: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m2, 37.5 mg/m2, and 50 mg/m2, on days 1 and 8 of a 21-day cycle. Main Outcomes and Measures: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). Results: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m2. The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%. Conclusions and Relevance: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers.

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