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INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG)
BACKGROUND: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine ki...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945618/ https://www.ncbi.nlm.nih.gov/pubmed/36814222 http://dx.doi.org/10.1186/s12885-023-10642-7 |
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author | Lam, Lyn Ley Pavlakis, Nick Shitara, Kohei Sjoquist, Katrin M. Martin, Andrew J. Yip, Sonia Kang, Yoon-Koo Bang, Yung-Jue Chen, Li-Tzong Moehler, Markus Bekaii-Saab, Tanios Alcindor, Thierry O’Callaghan, Christopher J. Tebbutt, Niall C. Hague, Wendy Chan, Howard Rha, Sun Young Lee, Keun-Wook Gebski, Val Jaworski, Anthony Zalcberg, John Price, Timothy Simes, John Goldstein, David |
author_facet | Lam, Lyn Ley Pavlakis, Nick Shitara, Kohei Sjoquist, Katrin M. Martin, Andrew J. Yip, Sonia Kang, Yoon-Koo Bang, Yung-Jue Chen, Li-Tzong Moehler, Markus Bekaii-Saab, Tanios Alcindor, Thierry O’Callaghan, Christopher J. Tebbutt, Niall C. Hague, Wendy Chan, Howard Rha, Sun Young Lee, Keun-Wook Gebski, Val Jaworski, Anthony Zalcberg, John Price, Timothy Simes, John Goldstein, David |
author_sort | Lam, Lyn Ley |
collection | PubMed |
description | BACKGROUND: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO). METHODS/DESIGN: INTEGRATE II (INTEGRATE IIa and IIb) platform comprises two international phase III randomised controlled trials (RCT) with 2:1 randomisation in favor of experimental intervention. INTEGRATE IIa (double-blind) compares regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle to placebo. INTEGRATE IIb (open label) compares REGONIVO, regorafenib 90 mg days 1 to 21 in combination with intravenous nivolumab 240 mg days 1 and 15 each 28-day cycle with investigator’s choice of chemotherapy (control). Treatment continues until disease progression or intolerable adverse events as per protocol. Eligible participants include adults with AGOC who have failed two or more lines of treatment. Stratification is by location of tumour (INTEGRATE IIa only), geographic region, prior VEGF inhibitor and prior immunotherapy use (INTEGRATE IIb only). Primary endpoint is overall survival. Secondary endpoints are progression free survival, objective response rate, quality of life, and safety. Tertiary/correlative objectives include biomarker and pharmacokinetic evaluation. DISCUSSION: INTEGRATE II provides a platform to evaluate the clinical utility of regorafenib alone, as well as regorafenib in combination with nivolumab in treatment of participants with refractory AGOC. TRIAL REGISTRATION: INTEGRATE IIa prospectively registered 1 April 2016 Australia New Zealand Clinical Trial Registry: ACTRN12616000420448 (ClinicalTrials.gov NCT02773524). INTEGRATE IIb prospectively registered 10 May 2021 ClinicalTrials.gov: NCT04879368. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10642-7. |
format | Online Article Text |
id | pubmed-9945618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99456182023-02-23 INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) Lam, Lyn Ley Pavlakis, Nick Shitara, Kohei Sjoquist, Katrin M. Martin, Andrew J. Yip, Sonia Kang, Yoon-Koo Bang, Yung-Jue Chen, Li-Tzong Moehler, Markus Bekaii-Saab, Tanios Alcindor, Thierry O’Callaghan, Christopher J. Tebbutt, Niall C. Hague, Wendy Chan, Howard Rha, Sun Young Lee, Keun-Wook Gebski, Val Jaworski, Anthony Zalcberg, John Price, Timothy Simes, John Goldstein, David BMC Cancer Study Protocol BACKGROUND: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO). METHODS/DESIGN: INTEGRATE II (INTEGRATE IIa and IIb) platform comprises two international phase III randomised controlled trials (RCT) with 2:1 randomisation in favor of experimental intervention. INTEGRATE IIa (double-blind) compares regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle to placebo. INTEGRATE IIb (open label) compares REGONIVO, regorafenib 90 mg days 1 to 21 in combination with intravenous nivolumab 240 mg days 1 and 15 each 28-day cycle with investigator’s choice of chemotherapy (control). Treatment continues until disease progression or intolerable adverse events as per protocol. Eligible participants include adults with AGOC who have failed two or more lines of treatment. Stratification is by location of tumour (INTEGRATE IIa only), geographic region, prior VEGF inhibitor and prior immunotherapy use (INTEGRATE IIb only). Primary endpoint is overall survival. Secondary endpoints are progression free survival, objective response rate, quality of life, and safety. Tertiary/correlative objectives include biomarker and pharmacokinetic evaluation. DISCUSSION: INTEGRATE II provides a platform to evaluate the clinical utility of regorafenib alone, as well as regorafenib in combination with nivolumab in treatment of participants with refractory AGOC. TRIAL REGISTRATION: INTEGRATE IIa prospectively registered 1 April 2016 Australia New Zealand Clinical Trial Registry: ACTRN12616000420448 (ClinicalTrials.gov NCT02773524). INTEGRATE IIb prospectively registered 10 May 2021 ClinicalTrials.gov: NCT04879368. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10642-7. BioMed Central 2023-02-22 /pmc/articles/PMC9945618/ /pubmed/36814222 http://dx.doi.org/10.1186/s12885-023-10642-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Study Protocol Lam, Lyn Ley Pavlakis, Nick Shitara, Kohei Sjoquist, Katrin M. Martin, Andrew J. Yip, Sonia Kang, Yoon-Koo Bang, Yung-Jue Chen, Li-Tzong Moehler, Markus Bekaii-Saab, Tanios Alcindor, Thierry O’Callaghan, Christopher J. Tebbutt, Niall C. Hague, Wendy Chan, Howard Rha, Sun Young Lee, Keun-Wook Gebski, Val Jaworski, Anthony Zalcberg, John Price, Timothy Simes, John Goldstein, David INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title | INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title_full | INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title_fullStr | INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title_full_unstemmed | INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title_short | INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG) |
title_sort | integrate ii: randomised phase iii controlled trials of regorafenib containing regimens versus standard of care in refractory advanced gastro-oesophageal cancer (agoc): a study by the australasian gastro-intestinal trials group (agitg) |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945618/ https://www.ncbi.nlm.nih.gov/pubmed/36814222 http://dx.doi.org/10.1186/s12885-023-10642-7 |
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