Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)
Abstract Background Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-08-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11199-1 |
| _version_ | 1797452316504227840 |
|---|---|
| author | Naoki Takahashi Hiroki Hara Kengo Nagashima Kenro Hirata Toshiki Masuishi Toshihiko Matsumoto Hisato Kawakami Kentaro Yamazaki Shuichi Hironaka Narikazu Boku Kei Muro |
| author_facet | Naoki Takahashi Hiroki Hara Kengo Nagashima Kenro Hirata Toshiki Masuishi Toshihiko Matsumoto Hisato Kawakami Kentaro Yamazaki Shuichi Hironaka Narikazu Boku Kei Muro |
| author_sort | Naoki Takahashi |
| collection | DOAJ |
| description | Abstract Background Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma. Methods This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m2 twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70. Discussion This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer. Trial registration jRCTs041220120. |
| first_indexed | 2024-03-09T15:06:49Z |
| format | Article |
| id | doaj.art-7e4e091163904bb1a0330ed3bafd6354 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T15:06:49Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7e4e091163904bb1a0330ed3bafd63542023-11-26T13:37:18ZengBMCBMC Cancer1471-24072023-08-012311810.1186/s12885-023-11199-1Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)Naoki Takahashi0Hiroki Hara1Kengo Nagashima2Kenro Hirata3Toshiki Masuishi4Toshihiko Matsumoto5Hisato Kawakami6Kentaro Yamazaki7Shuichi Hironaka8Narikazu Boku9Kei Muro10Department of Gastroenterology, Saitama Cancer CenterDepartment of Gastroenterology, Saitama Cancer CenterBiostatistics Unit, Clinical and Translational Research Center, Keio University HospitalDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of MedicineDepartment of Clinical Oncology, Aichi Cancer Center HospitalCancer Treatment Center, Kansai Medical UniversityDepartment of Medical Oncology, Faculty of Medicine, Kindai UniversityDepartment of Gastrointestinal Oncology, Shizuoka Cancer CenterDepartment of Medical Oncology, Faculty of Medicine, Kyorin UniversityDepartment of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of TokyoDepartment of Clinical Oncology, Aichi Cancer Center HospitalAbstract Background Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma. Methods This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m2 twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70. Discussion This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer. Trial registration jRCTs041220120.https://doi.org/10.1186/s12885-023-11199-1Trifluridine/tipiracilRamucirumabGastric cancerAngiogenesis inhibitorEsophagogastric Junction adenocarcinoma |
| spellingShingle | Naoki Takahashi Hiroki Hara Kengo Nagashima Kenro Hirata Toshiki Masuishi Toshihiko Matsumoto Hisato Kawakami Kentaro Yamazaki Shuichi Hironaka Narikazu Boku Kei Muro Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) BMC Cancer Trifluridine/tipiracil Ramucirumab Gastric cancer Angiogenesis inhibitor Esophagogastric Junction adenocarcinoma |
| title | Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) |
| title_full | Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) |
| title_fullStr | Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) |
| title_full_unstemmed | Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) |
| title_short | Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) |
| title_sort | randomised phase ii trial of trifluridine tipiracil ftd tpi plus ramucirumab ram versus trifluridine tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma retrieve study wjog15822g |
| topic | Trifluridine/tipiracil Ramucirumab Gastric cancer Angiogenesis inhibitor Esophagogastric Junction adenocarcinoma |
| url | https://doi.org/10.1186/s12885-023-11199-1 |
| work_keys_str_mv | AT naokitakahashi randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT hirokihara randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT kengonagashima randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT kenrohirata randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT toshikimasuishi randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT toshihikomatsumoto randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT hisatokawakami randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT kentaroyamazaki randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT shuichihironaka randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT narikazuboku randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g AT keimuro randomisedphaseiitrialoftrifluridinetipiracilftdtpiplusramucirumabramversustrifluridinetipiracilforpreviouslytreatedpatientswithadvancedgastricoresophagogastricjunctionadenocarcinomaretrievestudywjog15822g |