Retrospective Study of Trabectedin in Soft Tissue Sarcomas

Sarcoma, Soft Tissue Clinical Trial

— TrObs  

Official title:

Trabectedin in Soft Tissue Sarcomas. A Retrospective Observational Analysis (TrObs)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02793050
• Other study ID #: ISG TrObs
• Status: Completed
• Start date: June 15, 2016
• Est. completion date: October 2, 2018

Study information

• Verified date: May 2019
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an independent, observational, retrospective post marketing study on the use of trabectedin in a clinical setting.

A data collection on the clinical use of the drug will help to improve knowledge and might contribute to optimize the clinical use of the drug.

Description:

This is a national, multi-centre observational retrospective and prospective chart review study of treatment patterns and clinical outcomes in a subset of patients with Soft Tissue Sarcoma who received trabectedin as per licensed indication.

In the absence of availability of existing databases, a retrospective chart review design was selected.

It is anticipated that the medical charts will contain the information required to answer study objectives. This chart review study will be conducted in 25 sites in Italy An estimated total of 900 charts will be abstracted. This study requires no intervention or interference with standard medical care, and thus it will not affect patient treatment.

The study is sponsored by Italian Sarcoma Group Charts of patients who initiated trabectedin as part of the approved treatment for a Soft Tissue Sarcoma , will be identified by site staff. Each identified chart will be assigned a unique study identification number. Site staff will review the medical charts for all identified patients to determine patient eligibility. Those patients who meet eligibility criteria will be enrolled into the final study cohort as subject.

Data from subject medical charts will be abstracted by local site study staff and entered at the site into an electronic data capture (EDC) system. The system will also facilitate the monitoring of the completeness and quality of study data as the study data accrue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 510
• Est. completion date: October 2, 2018
• Est. primary completion date: October 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who received trabectedin according to the approved indication in the period January 2010 December 2015

Exclusion Criteria:

• Trabectedin started before January 2010 and after December 2015

• Participation into clinical trials with trabectedin

• Clinical chart missing, empty, or not retrievable.

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Drug:
• Trabectedin
Collection of data on the clinical use of Trabectedin

Locations

Country	Name	City	State
Italy	A.O. SS Antonio e Biagio e Cesare Arrigo	Alessandria	AL
Italy	Centro di Riferimento Oncologico di Aviano	Aviano	PD
Italy	Istituto Tumori Giovanni Paolo II	Bari	BA
Italy	Ospedali Riuniti di Bergamo	Bergamo	BG
Italy	Istituto Ortopedico Rizzoli	Bologna
Italy	Policlinico S.Orsola Malpighi - Unit of Medical Oncology	Bologna
Italy	Pres.Ospedal.Spedali Civili Brescia -	Brescia (BS)
Italy	Ospedale Oncologico A. Businco	Cagliari	CA
Italy	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo	Torino
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST	Meldola	FC
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Irccs Istituto Nazionale Dei Tumori (Int)	Milano (MI)
Italy	Azienda Ospedaliero-Universitaria di Modena - Policlinico	Modena
Italy	Irccs Istituto Nazionale Tumori Fondazione Pascale -	Napoli (NA)
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	Azienda Ospedaliera Universitaria Paolo Giaccone	Palermo	PA
Italy	Azienda Ospedaliera Universitaria Santa Chiara	Pisa	PI
Italy	Ospedale Misericordia e Dolce Ist. Toscano Tumori, Az. USL4	Prato
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera Di Reggio Emilia	Reggio EMilia
Italy	Fondazione Policlinico Universitario "Agostino Gemelli"	Roma
Italy	Policlinico Universitario Campus Biomedico	Roma	RM
Italy	Istituto Regina Elena - IFO	Rome
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino
Italy	Presidio Sanitario Gradenigo Di Torino	Torino (TO)

Sponsors (1)

Lead Sponsor	Collaborator
Italian Sarcoma Group

Country where clinical trial is conducted

Italy, 

References & Publications (18)

Blay JY, Italiano A, Ray-Coquard I, Le Cesne A, Duffaud F, Rios M, Collard O, Bertucci F, Bompas E, Isambert N, Chaigneau L, Cassier P, Bui B, Decanter G, Derbel O, Coindre JM, Zintl P, Badri N, Penel N. Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program. BMC Cancer. 2013 Feb 6;13:64. doi: 10.1186/1471-2407-13-64. — View Citation

Bonfanti M, La Valle E, Fernandez Sousa Faro JM, Faircloth G, Caretti G, Mantovani R, D'Incalci M. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des. 1999 Jun;14(3):179-86. — View Citation

D'Incalci M, Badri N, Galmarini CM, Allavena P. Trabectedin, a drug acting on both cancer cells and the tumour microenvironment. Br J Cancer. 2014 Aug 12;111(4):646-50. doi: 10.1038/bjc.2014.149. Epub 2014 Apr 22. Review. — View Citation

Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. doi: 10.1200/JCO.2008.21.0088. Epub 2009 Aug 3. — View Citation

Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001 Jan;37(1):97-105. — View Citation

ESMO/European Sarcoma Network Working Group. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25 Suppl 3:iii102-12. doi: 10.1093/annonc/mdu254. Erratum in: Ann Oncol. 2015 Sep;26 Suppl 5:v174-7. — View Citation

Fayette J, Coquard IR, Alberti L, Boyle H, Méeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchère D, Blay JY. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol. 2006 Jul;18(4):347-53. Review. — View Citation

Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol. 2005 Aug 20;23(24):5484-92. — View Citation

Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 2004 Apr 15;22(8):1480-90. — View Citation

Grosso F, Sanfilippo R, Virdis E, Piovesan C, Collini P, Dileo P, Morosi C, Tercero JC, Jimeno J, D'Incalci M, Gronchi A, Pilotti S, Casali PG. Trabectedin in myxoid liposarcomas (MLS): a long-term analysis of a single-institution series. Ann Oncol. 2009 Aug;20(8):1439-44. doi: 10.1093/annonc/mdp004. Epub 2009 May 22. — View Citation

Italiano A, Mathoulin-Pelissier S, Cesne AL, Terrier P, Bonvalot S, Collin F, Michels JJ, Blay JY, Coindre JM, Bui B. Trends in survival for patients with metastatic soft-tissue sarcoma. Cancer. 2011 Mar 1;117(5):1049-54. doi: 10.1002/cncr.25538. Epub 2010 Oct 13. — View Citation

Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. doi: 10.1016/S1470-2045(14)70063-4. Epub 2014 Mar 5. — View Citation

Le Cesne A, Blay JY, Domont J, Tresch-Bruneel E, Chevreau C, Bertucci F, Delcambre C, Saada-Bouzid E, Piperno-Neumann S, Bay JO, Mir O, Ray-Coquard I, Ryckewaert T, Valentin T, Isambert N, Italiano A, Clisant S, Penel N. Interruption versus continuation of trabectedin in patients with soft-tissue sarcoma (T-DIS): a randomised phase 2 trial. Lancet Oncol. 2015 Mar;16(3):312-9. doi: 10.1016/S1470-2045(15)70031-8. Epub 2015 Feb 11. — View Citation

Le Cesne A, Ray-Coquard I, Duffaud F, Chevreau C, Penel N, Bui Nguyen B, Piperno-Neumann S, Delcambre C, Rios M, Chaigneau L, Le Maignan C, Guillemet C, Bertucci F, Bompas E, Linassier C, Olivier T, Kurtz JE, Even C, Cousin P, Yves Blay J; French Sarcoma Group. Trabectedin in patients with advanced soft tissue sarcoma: a retrospective national analysis of the French Sarcoma Group. Eur J Cancer. 2015 Apr;51(6):742-50. doi: 10.1016/j.ejca.2015.01.006. Epub 2015 Feb 23. — View Citation

Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry. 1996 Oct 15;35(41):13303-9. — View Citation

Samuels BL, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser PE, Schuetze S, Li J, Aymes A, Demetri GD. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013 Jun;24(6):1703-9. doi: 10.1093/annonc/mds659. Epub 2013 Feb 5. — View Citation

Sleijfer S, Ouali M, van Glabbeke M, Krarup-Hansen A, Rodenhuis S, Le Cesne A, Hogendoorn PC, Verweij J, Blay JY. Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer. 2010 Jan;46(1):72-83. doi: 10.1016/j.ejca.2009.09.022. — View Citation

Stiller CA, Trama A, Brewster DH, Verne J, Bouchardy C, Navarro C, Chirlaque MD, Marcos-Gragera R, Visser O, Serraino D, Weiderpass E, Dei Tos AP, Ascoli V; RARECARE Working Group. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project. Cancer Epidemiol. 2014 Dec;38(6):670-8. doi: 10.1016/j.canep.2014.09.009. Epub 2014 Oct 22. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Histology related treatment response	Number of patient who did not progress based on the different Soft Tissue Sarcoma histology sub-type	after 6 months from trabectedin start date
Primary	Post-trabectedin received treatment	Number of chemotherapy lines received after trabectedin given according to the approved indication	Through treatment completion, an average of 24 month
Secondary	Tumor response	Percent of patients with non progressing disease at 6 months	after 6 months from trabectedin start date
Secondary	Trabectedin dose modification	Describe trabectedin treatment experience in term of dose for patients with Soft Tissue Sarcoma treated with trabectedin as per market indication	Through treatment completion, an average of 24 month
Secondary	Progression-free survival	Describe progression-free survival (PFS) for patients with Soft Tissue Sarcoma who received trabectedin.	after 5 years and 3 years from trabectedin start date
Secondary	Trabectedin safety profile	Describe trabectedin safety profile in terms of number of participants with treatment-related adverse events as assessed by CTCAE v4.0 tha caused treatment discontinuation	Through treatment completion, an average of 24 month
Secondary	Overall survival	Describe overall survival (OS) for patients with Soft Tissue Sarcoma who received trabectedin.	after 5 years and 3 years from trabectedin start date