Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT)
Abstract Background Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have syner...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-01-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-019-6503-6 |
| _version_ | 1818383523808018432 |
|---|---|
| author | Sebastian C. Schmid Florestan J. Koll Claus Rödel Philipp Maisch Andreas Sauter Franziska Beckert Anna Seitz Hubert Kübler Michael Flentje Felix Chun Stephanie E. Combs Kilian Schiller Jürgen E. Gschwend Margitta Retz |
| author_facet | Sebastian C. Schmid Florestan J. Koll Claus Rödel Philipp Maisch Andreas Sauter Franziska Beckert Anna Seitz Hubert Kübler Michael Flentje Felix Chun Stephanie E. Combs Kilian Schiller Jürgen E. Gschwend Margitta Retz |
| author_sort | Sebastian C. Schmid |
| collection | DOAJ |
| description | Abstract Background Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. Methods Study design: “RACE IT” (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11–15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. Discussion This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. Trial registration Protocol Code RACE IT: AB 65/18; EudraCT: 2018–001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018. |
| first_indexed | 2024-12-14T03:07:44Z |
| format | Article |
| id | doaj.art-83da227f8a00483e9c4910ad40b9d1ef |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-14T03:07:44Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-83da227f8a00483e9c4910ad40b9d1ef2022-12-21T23:19:21ZengBMCBMC Cancer1471-24072020-01-012011910.1186/s12885-019-6503-6Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT)Sebastian C. Schmid0Florestan J. Koll1Claus Rödel2Philipp Maisch3Andreas Sauter4Franziska Beckert5Anna Seitz6Hubert Kübler7Michael Flentje8Felix Chun9Stephanie E. Combs10Kilian Schiller11Jürgen E. Gschwend12Margitta Retz13Department of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Radiation Oncology, University of FrankfurtDepartment of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Diagnostic and Interventional Radiology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Urology, University of WürzburgDepartment of Urology, University of WürzburgDepartment of Radiation Oncology, University of WürzburgDepartment of Urology, University of FrankfurtDepartment of Radiation Oncology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Radiation Oncology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichDepartment of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of MunichAbstract Background Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. Methods Study design: “RACE IT” (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11–15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. Discussion This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. Trial registration Protocol Code RACE IT: AB 65/18; EudraCT: 2018–001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018.https://doi.org/10.1186/s12885-019-6503-6Bladder cancerUrothelial cancerTransitional cell carcinomaLocally advancedImmunotherapyRadiotherapy |
| spellingShingle | Sebastian C. Schmid Florestan J. Koll Claus Rödel Philipp Maisch Andreas Sauter Franziska Beckert Anna Seitz Hubert Kübler Michael Flentje Felix Chun Stephanie E. Combs Kilian Schiller Jürgen E. Gschwend Margitta Retz Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) BMC Cancer Bladder cancer Urothelial cancer Transitional cell carcinoma Locally advanced Immunotherapy Radiotherapy |
| title | Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) |
| title_full | Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) |
| title_fullStr | Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) |
| title_full_unstemmed | Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) |
| title_short | Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer – study protocol of a prospective, single arm, multicenter phase II trial (RACE IT) |
| title_sort | radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer study protocol of a prospective single arm multicenter phase ii trial race it |
| topic | Bladder cancer Urothelial cancer Transitional cell carcinoma Locally advanced Immunotherapy Radiotherapy |
| url | https://doi.org/10.1186/s12885-019-6503-6 |
| work_keys_str_mv | AT sebastiancschmid radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT florestanjkoll radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT clausrodel radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT philippmaisch radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT andreassauter radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT franziskabeckert radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT annaseitz radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT hubertkubler radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT michaelflentje radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT felixchun radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT stephanieecombs radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT kilianschiller radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT jurgenegschwend radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit AT margittaretz radiationtherapybeforeradicalcystectomycombinedwithimmunotherapyinlocallyadvancedbladdercancerstudyprotocolofaprospectivesinglearmmulticenterphaseiitrialraceit |