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)
Abstract 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 tyr...
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BMC
2023-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-10642-7 |
| _version_ | 1797864444766715904 |
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| author | Lyn Ley Lam Nick Pavlakis Kohei Shitara Katrin M. Sjoquist Andrew J. Martin Sonia Yip Yoon-Koo Kang Yung-Jue Bang Li-Tzong Chen Markus Moehler Tanios Bekaii-Saab Thierry Alcindor Christopher J. O’Callaghan Niall C. Tebbutt Wendy Hague Howard Chan Sun Young Rha Keun-Wook Lee Val Gebski Anthony Jaworski John Zalcberg Timothy Price John Simes David Goldstein |
| author_facet | Lyn Ley Lam Nick Pavlakis Kohei Shitara Katrin M. Sjoquist Andrew J. Martin Sonia Yip Yoon-Koo Kang Yung-Jue Bang Li-Tzong Chen Markus Moehler Tanios Bekaii-Saab Thierry Alcindor Christopher J. O’Callaghan Niall C. Tebbutt Wendy Hague Howard Chan Sun Young Rha Keun-Wook Lee Val Gebski Anthony Jaworski John Zalcberg Timothy Price John Simes David Goldstein |
| author_sort | Lyn Ley Lam |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:53:10Z |
| format | Article |
| id | doaj.art-b8e8b11dcadf410b83fe55a98f0861f4 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:53:10Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b8e8b11dcadf410b83fe55a98f0861f42023-03-22T11:34:25ZengBMCBMC Cancer1471-24072023-02-0123111210.1186/s12885-023-10642-7INTEGRATE 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)Lyn Ley Lam0Nick Pavlakis1Kohei Shitara2Katrin M. Sjoquist3Andrew J. Martin4Sonia Yip5Yoon-Koo Kang6Yung-Jue Bang7Li-Tzong Chen8Markus Moehler9Tanios Bekaii-Saab10Thierry Alcindor11Christopher J. O’Callaghan12Niall C. Tebbutt13Wendy Hague14Howard Chan15Sun Young Rha16Keun-Wook Lee17Val Gebski18Anthony Jaworski19John Zalcberg20Timothy Price21John Simes22David Goldstein23NHMRC Clinical Trials Centre, University of SydneyRoyal North Shore HospitalNational Cancer Centre Hospital EastNHMRC Clinical Trials Centre, University of SydneyNHMRC Clinical Trials Centre, University of SydneyNHMRC Clinical Trials Centre, University of SydneyAsan Medical CentreSeoul National University College of MedicineCollege of Medicine, Kaohsiung Medical UniversityUniversity Medical Centre MainzMayo Clinic Comprehensive Cancer CentreMcGill University Health CentreOlivia Newton-John Cancer Wellness & Research CentreOlivia Newton-John Cancer Wellness & Research CentreNHMRC Clinical Trials Centre, University of SydneyCalvary Mater NewcastleYonsei Cancer Centre, Yonsei University Health SystemSeoul National University College of MedicineNHMRC Clinical Trials Centre, University of SydneyNHMRC Clinical Trials Centre, University of SydneyMonash University MelbourneThe Queen Elizabeth HospitalNHMRC Clinical Trials Centre, University of SydneyPrince of Wales HospitalAbstract 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.https://doi.org/10.1186/s12885-023-10642-7Advanced gastro-oesophageal cancerRegorafenibNivolumabTyrosine kinase inhibitorClinical trial |
| spellingShingle | Lyn Ley Lam Nick Pavlakis Kohei Shitara Katrin M. Sjoquist Andrew J. Martin Sonia Yip Yoon-Koo Kang Yung-Jue Bang Li-Tzong Chen Markus Moehler Tanios Bekaii-Saab Thierry Alcindor Christopher J. O’Callaghan Niall C. Tebbutt Wendy Hague Howard Chan Sun Young Rha Keun-Wook Lee Val Gebski Anthony Jaworski John Zalcberg Timothy Price John Simes David Goldstein 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) BMC Cancer Advanced gastro-oesophageal cancer Regorafenib Nivolumab Tyrosine kinase inhibitor Clinical trial |
| 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 | Advanced gastro-oesophageal cancer Regorafenib Nivolumab Tyrosine kinase inhibitor Clinical trial |
| url | https://doi.org/10.1186/s12885-023-10642-7 |
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