Clinical Study in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT) ISG-TULIPS

Summary

Patients participating in this study have DSRCT that has spread locally or to other parts of the body and can no longer be surgically removed without causing significant harm. Treatment will continue until the tumor progresses further, severe side effects occur, or either patient or investigator decision. In addition, patients may participate in an optional biological study. The study will analyze the tumor's genes and the molecules related to them. By studying genes and their products, the investigators can better understand the behavior of the tumor and how the body responds to therapies.

Timeline

Start

2025-11-21

Primary completion

2030-10-01

Completion

2030-10-01

Publications

• Background Jayakrishnan T, Moll R, Sandhu A, Sanguino A, Kaur G, Mao S. Desmoplastic Small Round-cell Tumor: Retrospective Review of Institutional Data and Literature Review. Anticancer Res. 2021 Aug;41(8):3859-3866. doi: 10.21873/anticanres.15179.
• Background Hayes-Jordan AA, Coakley BA, Green HL, Xiao L, Fournier KF, Herzog CE, Ludwig JA, McAleer MF, Anderson PM, Huh WW. Desmoplastic Small Round Cell Tumor Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Results of a Phase 2 Trial. Ann Surg Oncol. 2018 Apr;25(4):872-877. doi: 10.1245/s10434-018-6333-9. Epub 2018 Jan 30.
• Background Rosoff PM, Bayliff S. Successful clinical response to irinotecan in desmoplastic round blue cell tumor. Med Pediatr Oncol. 1999 Nov;33(5):500-3. doi: 10.1002/(sici)1096-911x(199911)33:53.0.co;2-x. No abstract available.
• Background Honore C, Amroun K, Vilcot L, Mir O, Domont J, Terrier P, Le Cesne A, Le Pechoux C, Bonvalot S. Abdominal desmoplastic small round cell tumor: multimodal treatment combining chemotherapy, surgery, and radiotherapy is the best option. Ann Surg Oncol. 2015 Apr;22(4):1073-9. doi: 10.1245/s10434-014-4123-6. Epub 2014 Oct 10.
• Background Stacchiotti S, Frezza AM, Blay JY, Baldini EH, Bonvalot S, Bovee JVMG, Callegaro D, Casali PG, Chiang RC, Demetri GD, Demicco EG, Desai J, Eriksson M, Gelderblom H, George S, Gounder MM, Gronchi A, Gupta A, Haas RL, Hayes-Jardon A, Hohenberger P, Jones KB, Jones RL, Kasper B, Kawai A, Kirsch DG, Kleinerman ES, Le Cesne A, Lim J, Chirlaque Lopez MD, Maestro R, Marcos-Gragera R, Martin Broto J, Matsuda T, Mir O, Patel SR, Raut CP, Razak ARA, Reed DR, Rutkowski P, Sanfilippo RG, Sbaraglia M, Schaefer IM, Strauss DC, Sundby Hall K, Tap WD, Thomas DM, van der Graaf WTA, van Houdt WJ, Visser O, von Mehren M, Wagner AJ, Wilky BA, Won YJ, Fletcher CDM, Dei Tos AP, Trama A. Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021 Aug 15;127(16):2934-2942. doi: 10.1002/cncr.33618. Epub 2021 Apr 28.
• Background Saab R, Khoury JD, Krasin M, Davidoff AM, Navid F. Desmoplastic small round cell tumor in childhood: the St. Jude Children's Research Hospital experience. Pediatr Blood Cancer. 2007 Sep;49(3):274-9. doi: 10.1002/pbc.20893.
• Background Liu KX, Collins NB, Greenzang KA, Furutani E, Campbell K, Groves A, Mullen EA, Shusterman S, Spidle J, Marcus KJ, Weil BR, Weldon CB, Frazier AL, Janeway KA, O'Neill AF, Mack JW, DuBois SG, Shulman DS. The use of interval-compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor. Pediatr Blood Cancer. 2020 Oct;67(10):e28559. doi: 10.1002/pbc.28559. Epub 2020 Jul 19.
• Background Verret B, Honore C, Dumont S, Terrier P, Adam J, Cavalcanti A, Sourrouille I, Klausner G, Ahlenc-Gelas M, Kiavue N, Domitrescu G, El Amarti L, Mir O, Le Cesne A. Trabectedin in advanced desmoplastic round cell tumors: a retrospective single-center series. Anticancer Drugs. 2017 Jan;28(1):116-119. doi: 10.1097/CAD.0000000000000435.
• Background Giani C, Radaelli S, Miceli R, Gandola L, Sangalli C, Frezza AM, Provenzano S, Pasquali S, Bertulli R, Fiore M, Callegaro D, Casanova M, Chiaravalli S, Collini P, Dagrada GP, Morosi C, Zaffaroni N, Casali PG, Ferrari A, Gronchi A, Stacchiotti S. Long-term survivors with desmoplastic small round cell tumor (DSRCT): Results from a retrospective single-institution case series analysis. Cancer Med. 2023 May;12(9):10694-10703. doi: 10.1002/cam4.5829. Epub 2023 Mar 23.
• Background Brunetti AE, Delcuratolo S, Lorusso V, Palermo L, Di Giorgio A, Pisconti S, Silvestris N. Third-line trabectedin for a metastatic desmoplastic small round cell tumour treated with multimodal therapy. Anticancer Res. 2014 Jul;34(7):3683-8.
• Background Leal JF, Martinez-Diez M, Garcia-Hernandez V, Moneo V, Domingo A, Bueren-Calabuig JA, Negri A, Gago F, Guillen-Navarro MJ, Aviles P, Cuevas C, Garcia-Fernandez LF, Galmarini CM. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol. 2010 Nov;161(5):1099-110. doi: 10.1111/j.1476-5381.2010.00945.x.
• Background Lettieri CK, Garcia-Filion P, Hingorani P. Incidence and outcomes of desmoplastic small round cell tumor: results from the surveillance, epidemiology, and end results database. J Cancer Epidemiol. 2014;2014:680126. doi: 10.1155/2014/680126. Epub 2014 Nov 5.
• Background Zuco V, Pasquali S, Tortoreto M, Percio S, Doldi V, Barisella M, Collini P, Dagrada GP, Brich S, Gasparini P, Fiore M, Casanova M, Frezza AM, Gronchi A, Stacchiotti S, Ferrari A, Zaffaroni N. Effectiveness of irinotecan plus trabectedin on a desmoplastic small round cell tumor patient-derived xenograft. Dis Model Mech. 2023 Jun 1;16(6):dmm049649. doi: 10.1242/dmm.049649. Epub 2023 Jun 14.
• Background Scheer M, Vokuhl C, Blank B, Hallmen E, von Kalle T, Munter M, Wessalowski R, Hartwig M, Sparber-Sauer M, Schlegel PG, Kramm CM, Kontny U, Spriewald B, Kegel T, Bauer S, Kazanowska B, Niggli F, Ladenstein R, Ljungman G, Jahnukainen K, Fuchs J, Bielack SS, Klingebiel T, Koscielniak E; Cooperative Weichteilsarkom Studiengruppe [CWS]. Desmoplastic small round cell tumors: Multimodality treatment and new risk factors. Cancer Med. 2019 Feb;8(2):527-542. doi: 10.1002/cam4.1940. Epub 2019 Jan 16.
• Background Stiles ZE, Dickson PV, Glazer ES, Murphy AJ, Davidoff AM, Behrman SW, Bishop MW, Martin MG, Deneve JL. Desmoplastic small round cell tumor: A nationwide study of a rare sarcoma. J Surg Oncol. 2018 Jun;117(8):1759-1767. doi: 10.1002/jso.25071. Epub 2018 Jun 7.
• Background Italiano A, Kind M, Cioffi A, Maki RG, Bui B. Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series. Target Oncol. 2013 Sep;8(3):211-213. doi: 10.1007/s11523-012-0251-8. Epub 2013 Jan 6.
• Background Van Glabbeke M, Verweij J, Judson I, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543-9. doi: 10.1016/s0959-8049(01)00398-7.
• Background Bisogno G, Ferrari A, Tagarelli A, Sorbara S, Chiaravalli S, Poli E, Scarzello G, De Corti F, Casanova M, Affinita MC. Integrating irinotecan in standard chemotherapy: A novel dose-density combination for high-risk pediatric sarcomas. Pediatr Blood Cancer. 2021 Jul;68(7):e28951. doi: 10.1002/pbc.28951. Epub 2021 Mar 10.
• Background Frezza AM, Whelan JS, Dileo P. Trabectedin for desmoplastic small round cell tumours: a possible treatment option? Clin Sarcoma Res. 2014 Apr 25;4:3. doi: 10.1186/2045-3329-4-3. eCollection 2014.
• Background Harlow ML, Chasse MH, Boguslawski EA, Sorensen KM, Gedminas JM, Kitchen-Goosen SM, Rothbart SB, Taslim C, Lessnick SL, Peck AS, Madaj ZB, Bowman MJ, Grohar PJ. Trabectedin Inhibits EWS-FLI1 and Evicts SWI/SNF from Chromatin in a Schedule-dependent Manner. Clin Cancer Res. 2019 Jun 1;25(11):3417-3429. doi: 10.1158/1078-0432.CCR-18-3511. Epub 2019 Feb 5.
• Background Lima M, Bouzid H, Soares DG, Selle F, Morel C, Galmarini CM, Henriques JA, Larsen AK, Escargueil AE. Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair. Oncotarget. 2016 May 3;7(18):25885-901. doi: 10.18632/oncotarget.8292.
• Background Harlow ML, Maloney N, Roland J, Guillen Navarro MJ, Easton MK, Kitchen-Goosen SM, Boguslawski EA, Madaj ZB, Johnson BK, Bowman MJ, D'Incalci M, Winn ME, Turner L, Hostetter G, Galmarini CM, Aviles PM, Grohar PJ. Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by Redistributing It within the Nucleus. Cancer Res. 2016 Nov 15;76(22):6657-6668. doi: 10.1158/0008-5472.CAN-16-0568. Epub 2016 Oct 3.
• Background Bailey K, Roth M, Weiser D, Gill J. High-Dose Chemotherapy with Stem Cell Rescue in Desmoplastic Small Round Cell Tumor: A Single-Institution Experience and Review of the Literature. Sarcoma. 2018 May 6;2018:1948093. doi: 10.1155/2018/1948093. eCollection 2018.
• Background Lopez-Gonzalez A, Cantos B, Tejerina E, Provencio M. Activity of trabectidin in desmoplastic small round cell tumor. Med Oncol. 2011 Dec;28 Suppl 1:S644-6. doi: 10.1007/s12032-010-9687-9. Epub 2010 Oct 7.
• Background Mello CA, Campos FAB, Santos TG, Silva MLG, Torrezan GT, Costa FD, Formiga MN, Nicolau U, Nascimento AG, Silva C, Curado MP, Nakagawa SA, Lopes A, Aguiar S Jr. Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy. Cancers (Basel). 2021 Jan 28;13(3):498. doi: 10.3390/cancers13030498.
• Background Ferreira EN, Barros BD, de Souza JE, Almeida RV, Torrezan GT, Garcia S, Krepischi AC, Mello CA, Cunha IW, Pinto CA, Soares FA, Dias-Neto E, Lopes A, de Souza SJ, Carraro DM. A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease. Hum Genomics. 2016 Nov 18;10(1):36. doi: 10.1186/s40246-016-0092-0.
• Background Devecchi A, De Cecco L, Dugo M, Penso D, Dagrada G, Brich S, Stacchiotti S, Sensi M, Canevari S, Pilotti S. The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial-mesenchymal transition, and immune response. Cancer Commun (Lond). 2018 Nov 28;38(1):70. doi: 10.1186/s40880-018-0339-3.
• Background Frezza AM, Benson C, Judson IR, Litiere S, Marreaud S, Sleijfer S, Blay JY, Dewji R, Fisher C, van der Graaf W, Hayward L. Pazopanib in advanced desmoplastic small round cell tumours: a multi-institutional experience. Clin Sarcoma Res. 2014 Jul 29;4:7. doi: 10.1186/2045-3329-4-7. eCollection 2014.
• Background Santiago L, Daniels G, Wang D, Deng FM, Lee P. Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment. Am J Cancer Res. 2017 Jun 1;7(6):1389-1406. eCollection 2017.
• Background Gedminas JM, Kaufman R, Boguslawski EA, Gross AC, Adams M, Beddows I, Kitchen-Goosen SM, Roberts RD, Grohar PJ. Lurbinectedin Inhibits the EWS-WT1 Transcription Factor in Desmoplastic Small Round Cell Tumor. Mol Cancer Ther. 2022 Aug 2;21(8):1296-1305. doi: 10.1158/1535-7163.MCT-21-1003.
• Background Bisogno G, Ferrari A, Rosolen A, Alaggio R, Scarzello G, Garaventa A, Arcamone G, Carli M. Sequential intensified chemotherapy with stem cell rescue for children and adolescents with desmoplastic small round-cell tumor. Bone Marrow Transplant. 2010 May;45(5):907-11. doi: 10.1038/bmt.2009.248. Epub 2009 Oct 5.
• Background Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol. 2016 May;13(5):319-25. doi: 10.1038/nrclinonc.2015.222. Epub 2016 Jan 20.
• Background Uboldi S, Craparotta I, Colella G, Ronchetti E, Beltrame L, Vicario S, Marchini S, Panini N, Dagrada G, Bozzi F, Pilotti S, Galmarini CM, D'Incalci M, Gatta R. Mechanism of action of trabectedin in desmoplastic small round cell tumor cells. BMC Cancer. 2017 Feb 6;17(1):107. doi: 10.1186/s12885-017-3091-1.
• Background Ferrari A, Bergamaschi L, Chiaravalli S, Pecori E, Diletto B, Alessandro O, Giandini T, Livellara V, Sironi G, Casanova M. Multiagent chemotherapy including IrIVA regimen and maintenance therapy in the treatment of desmoplastic small round cell tumor. Tumori. 2022 Feb;108(1):93-97. doi: 10.1177/0300891621995250. Epub 2021 Feb 17.
• Background Hayes-Jordan A, Green HL, Lin H, Owusu-Agyemang P, Fitzgerald N, Arunkumar R, Mejia R, Okhuysen-Cawley R, Mauricio R, Fournier K, Ludwig J, Anderson P. Complete cytoreduction and HIPEC improves survival in desmoplastic small round cell tumor. Ann Surg Oncol. 2014 Jan;21(1):220-4. doi: 10.1245/s10434-013-3269-y. Epub 2013 Sep 18.
• Background Wei G, Shu X, Zhou Y, Liu X, Chen X, Qiu M. Intra-Abdominal Desmoplastic Small Round Cell Tumor: Current Treatment Options and Perspectives. Front Oncol. 2021 Sep 15;11:705760. doi: 10.3389/fonc.2021.705760. eCollection 2021.
• Background Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg. 2005 Jan;40(1):251-5. doi: 10.1016/j.jpedsurg.2004.09.046.
• Background Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, Garcia-Fernandez LF, Cuevas C, Allavena P, Erba E, D'Incalci M. Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis(R) (PM00104). Int J Cancer. 2013 Nov;133(9):2024-33. doi: 10.1002/ijc.28213. Epub 2013 May 25.
• Background Ferrari A, Chiaravalli S, Bergamaschi L, Nigro O, Livellara V, Sironi G, Gasparini P, Pasquali S, Zaffaroni N, Stacchiotti S, Morosi C, Massimino M, Casanova M. Trabectedin-irinotecan, a potentially promising combination in relapsed desmoplastic small round cell tumor: report of two cases. J Chemother. 2023 Apr;35(2):163-167. doi: 10.1080/1120009X.2022.2067706. Epub 2022 Apr 26.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background Hendricks A, Boerner K, Germer CT, Wiegering A. Desmoplastic Small Round Cell Tumors: A review with focus on clinical management and therapeutic options. Cancer Treat Rev. 2021 Feb;93:102140. doi: 10.1016/j.ctrv.2020.102140. Epub 2020 Dec 24.

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