Clinical trial NCT05700344: SOGUG-AVELUMAB_RWD
Official title: Multicentric, Observational Study to Evaluate Real World Data of Avelumab in First Line Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma, a SOGUG Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Urothelial Carcinoma
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
Collaborators: name: Adknoma Health Research
First posted: 2023-01-26
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with locally advanced or metastatic Urothelial Carcinoma who have not progressed after first line platinum-based treatment and who received or are receiving Avelumab as the first-line maintenance therapy in routine clinical practice.

Brief summary: The study goal is to evaluate the effectiveness in clinical practice of Avelumab as first line maintenance therapy in patients with locally advanced or metastatic Urothelial Carcinoma, who have not progressed after first line platinum-based treatment.

Study is performed at national hospitals from approximately 22 different sites and expecting to recruit 120 patients.

Patients understanding the nature of the study by providing their informed consent prior to participation.

* Patients of both sexes diagnosed with locally advanced or metastatic Urothelial Carcinoma, stage IV disease before first line with carboplatin/cisplatin-based chemotherapy. No disease progression after four-six cycles of ChT according to the Response Evaluation Criteria in Solid Tumor with a treatment free interval of 4-10 weeks before Avelumab initiation date.
* Patients who started Avelumab as maintenance therapy in first line after 21/Jan./2021 and before 27/Apr./2022 (both dates included).

Detailed description: Multicentre, observational, ambispective (retrospective and prospective) study to evaluate the real-world evidence of Avelumab as maintenance therapy in patients diagnosed with Urothelial Carcinoma (WHO classification) and previously treated with platinum-based treatment in first line. Study is performed at national hospitals from approximately 22 different sites and expecting to recruit 120 patients. Patients are selected based on the existing medical record of have been treated with Avelumab as maintenance therapy in first line before initiating the study (retrospective data); patients who continues receiving Avelumab after inclusion will also contribute to data collection until the end of treatment or end of study (prospective data).

According to mUC incidence and the selective inclusion criteria from this study of having initiated Avelumab as maintenance therapy in 1L between EMA approval date (Jan. 2021) and date of national reimbursement prize (Apr.2022), which is a narrow period of time to recruit the necessary number of candidates, therefore, prospective data from each participant patient will be a key to ensure the assessment of the study objective eventually.

Investigators will review the medical history of patients treated or under treatment of Avelumab and select chronologically those who matches the inclusion criteria. Patients will be informed during a regular follow up visit about the nature of the study and requested to sign the patient consent form once the decision of participating is made. At this point, the retrospective data from patients is collected (such as demographics, toxicity, anthropometrics, vital signs, comorbidities, hemogram, dosage modification etc.) previous adverse reactions (ARs) and serious adverse reaction (SARs) related to Avelumab. Included patients, that continues under Avelumab treatment will be monitored by investigators and prospective data from them will be collected during follow up visits and/or from electronic medical records (eMR).

Deceased patient who fulfils the inclusion criteria can be also included, being able to access to its clinical data at the beginning of the study according to Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation) and the Spanish Organic Law 3/2018 of 5th December, on the protection of personal data and digital rights. Additionally, the investigator team will consult in the eMR of deceased patients to ensure that they did not express in life opposition to the use of their data for investigational purposes.

Eligibility criteria: Inclusion Criteria:

* Patients understanding the nature of the study by providing their informed consent prior to participation.
* Patients of both sexes diagnosed with locally advanced or metastatic Urothelial Carcinoma, stage IV disease (AJCC ed. 8th, 2017) before first line with carboplatin/cisplatin-based chemotherapy (ChT). No disease progression after four-six cycles of ChT according to the Response Evaluation Criteria in Solid Tumor (RECIST 1.1) with a treatment free interval of 4-10 weeks before Avelumab initiation date.
* Patients who started Avelumab as maintenance therapy in first line after 21/Jan./2021 and before 27/Apr./2022 (both dates included).

Primary outcomes:
measure: Median progression free survival (mPFS)
timeFrame: Throughout the study period. Approximately 8 months
Secondary outcomes:
measure: Median overall survival (mOS)
timeFrame: Throughout the study period. Approximately 8 months
measure: Progression free survival rate at 12 months (PFS12)
timeFrame: Throughout the study period. Approximately 8 months
measure: Collection of any adverse reaction (AR) or serious adverse reaction (SAR)
timeFrame: Throughout the study period. Approximately 8 months
measure: Collection of any adverse event (AE) or serious adverse event (SAE)
timeFrame: Throughout the study period. Approximately 8 months
Other outcomes:
Locations:
city: Vigo
country: Spain
facility: Complexo Hospitalario Universitario de Vigo
state: Pontevedra
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario Albacete
city: Almería
country: Spain
facility: Complejo Hospitalario Torrecárdenas
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Castellón De La Plana
country: Spain
facility: Hospital Provincial de Castellón
city: Elche
country: Spain
facility: Hospital Universitario Vinalopó
city: Elda
country: Spain
facility: Hospital General Universitario de Elda
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Ourense
country: Spain
facility: Complexo Hospitalario Universitario Ourense
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Palencia
country: Spain
facility: Hospital Río Carrión
city: Sagunto
country: Spain
facility: Hospital Sagunto
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santiago De Compostela
country: Spain
facility: Complexo Hospitalario Universitario Santiago
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Universitario Politècnic La Fe
city: Villajoyosa
country: Spain
facility: Hospital Marina Baixa Villajosyosa
Study officials:
affiliation: Complejo Hospitalario Universitario A Coruña (CHUAC)
name: Áurea Molina
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario Universitario Ourense (CHOU)
name: Ovidio Fernández
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front Pharmacol. 2017 Feb 8;8:49. doi: 10.3389/fphar.2017.00049. eCollection 2017.
citation: Galsky MD, Balar AV, Black PC, Campbell MT, Dykstra GS, Grivas P, Gupta S, Hoimes CJ, Lopez LP, Meeks JJ, Plimack ER, Rosenberg JE, Shore N, Steinberg GD, Kamat AM. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of urothelial cancer. J Immunother Cancer. 2021 Jul;9(7):e002552. doi: 10.1136/jitc-2021-002552.
citation: Kim JW, Tomita Y, Trepel J, Apolo AB. Emerging immunotherapies for bladder cancer. Curr Opin Oncol. 2015 May;27(3):191-200. doi: 10.1097/CCO.0000000000000177.
citation: Morales-Barrera R, Suarez C, Gonzalez M, Valverde C, Serra E, Mateo J, Raventos C, Maldonado X, Morote J, Carles J. The future of bladder cancer therapy: Optimizing the inhibition of the fibroblast growth factor receptor. Cancer Treat Rev. 2020 Jun;86:102000. doi: 10.1016/j.ctrv.2020.102000. Epub 2020 Mar 13.
citation: Wolacewicz M, Hrynkiewicz R, Grywalska E, Suchojad T, Leksowski T, Rolinski J, Niedzwiedzka-Rystwej P. Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives. Cancers (Basel). 2020 May 7;12(5):1181. doi: 10.3390/cancers12051181.
citation: Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Duran I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Wu C, Campbell M, Matsangou M, Petrylak DP. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021 Mar 25;384(12):1125-1135. doi: 10.1056/NEJMoa2035807. Epub 2021 Feb 12.
citation: Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.
citation: Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, Plimack ER, Hahn NM, de Wit R, Pang L, Savage MJ, Perini RF, Keefe SM, Bajorin D, Bellmunt J. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Nov;18(11):1483-1492. doi: 10.1016/S1470-2045(17)30616-2. Epub 2017 Sep 26.
citation: Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JA, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.
citation: Bukhari N, Al-Shamsi HO, Azam F. Update on the Treatment of Metastatic Urothelial Carcinoma. ScientificWorldJournal. 2018 Jun 6;2018:5682078. doi: 10.1155/2018/5682078. eCollection 2018.
citation: von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. doi: 10.1200/JCO.2005.07.757.
citation: von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.
citation: Grivas P, Agarwal N, Pal S, Kalebasty AR, Sridhar SS, Smith J, Devgan G, Sternberg CN, Bellmunt J. Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: Applying clinical trial findings to clinical practice. Cancer Treat Rev. 2021 Jun;97:102187. doi: 10.1016/j.ctrv.2021.102187. Epub 2021 Mar 22.
citation: Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, Mega AE, Britten CD, Ravaud A, Mita AC, Safran H, Stinchcombe TE, Srdanov M, Gelb AB, Schlichting M, Chin K, Gulley JL. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J Clin Oncol. 2017 Jul 1;35(19):2117-2124. doi: 10.1200/JCO.2016.71.6795. Epub 2017 Apr 4.
citation: O'Donnell JC, Le TK, Dobrin R, Higashi M, Pereira A, Wagner S, Yang A, Hukkelhoven M. Evolving use of real-world evidence in the regulatory process: a focus on immuno-oncology treatment and outcomes. Future Oncol. 2021 Jan;17(3):333-347. doi: 10.2217/fon-2020-0591. Epub 2020 Oct 19.
citation: Cramer-van der Welle CM, Verschueren MV, Tonn M, Peters BJM, Schramel FMNH, Klungel OH, Groen HJM, van de Garde EMW; Santeon NSCLC Study Group. Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands. Sci Rep. 2021 Mar 18;11(1):6306. doi: 10.1038/s41598-021-85696-3.
citation: Pasello G, Pavan A, Attili I, Bortolami A, Bonanno L, Menis J, Conte P, Guarneri V. Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer. Cancer Treat Rev. 2020 Jul;87:102031. doi: 10.1016/j.ctrv.2020.102031. Epub 2020 May 16.
citation: Stewart M, Norden AD, Dreyer N, Henk HJ, Abernethy AP, Chrischilles E, Kushi L, Mansfield AS, Khozin S, Sharon E, Arunajadai S, Carnahan R, Christian JB, Miksad RA, Sakoda LC, Torres AZ, Valice E, Allen J. An Exploratory Analysis of Real-World End Points for Assessing Outcomes Among Immunotherapy-Treated Patients With Advanced Non-Small-Cell Lung Cancer. JCO Clin Cancer Inform. 2019 Jul;3:1-15. doi: 10.1200/CCI.18.00155.
citation: Aly A, Johnson C, Yang S, Botteman MF, Rao S, Hussain A. Overall survival, costs, and healthcare resource use by line of therapy in Medicare patients with newly diagnosed metastatic urothelial carcinoma. J Med Econ. 2019 Jul;22(7):662-670. doi: 10.1080/13696998.2019.1591424. Epub 2019 Mar 25.
citation: Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.