Study With Trabectedin Versus Adriamycin Plus Dacarbazine, in Patients With Advanced Solitary Fibrous Tumor

NCT03023124 | Completed Phase 2 DMC

• 1 other identifier: ISG STRADA
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

Brief Summary

Phase II randomized study for the comparison of trabectedin versus doxorubicin plus dacarbazine in patients with advanced solitary fibrous tumor

Conditions

Solitary Fibrous Tumors

Outcome Measures

Primary Outcomes (1)

• Overall Tumor Response Rate

  evaluate the activity of trabectedin and of adriamycin in combination with dacarbazine, according to Response Evaluation Criteria in Solid Tumor (RECIST), version 1.1

  From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 54 weeks.

Secondary Outcomes (7)

• Choi Response Rate

  week 6, week 12, week 18, then every 12 weeks up to 54 weeks

• Overall Survival (OS)

  From enrollment up to 5 years

• Progression Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks

• Clinical Benefit Rate (CBR)

  week 6, week 12, week 18, then every 12 weeks up to 54 weeks

• Response rate by RECIST after the cross over

  week 18, week 24, week 30, week 36 and then every 12 weeks up to 54 weeks

Study Arms (2)

Trabectedin

EXPERIMENTAL

trabectedin: 1.5 mg/m² - 1.3 mg/m² given in 24-hour continuous infusion every 21 days for 6 cycles

Drug: Trabectedin

Adriamycin and Dacarbazine

EXPERIMENTAL

Adriamycin: 75 mg/m2/day, bolus, day 1 every 21 days for 6 cycles Dacarbazine: 400 mg/m2/day, days 1, 2 every 21 days for 6 cycles

Drug: Adriamycin; Drug: Dacarbazine

Interventions

Trabectedin DRUG

Treatment with trabectedin repeated every 21 days for 6 cycles

Trabectedin

Adriamycin DRUG

Treatment with Adriamycin at day 1 every 21 days for 6 cycles

Adriamycin and Dacarbazine

Dacarbazine DRUG

Treatment with Dacarbazine at days 1 and 2 every 21 days for 6 cycles

Adriamycin and Dacarbazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.
• Age ≥18 years
• Histological centrally and molecularly confirmed diagnosis of solitary fibrous tumor (inclusive of the last available tumor sample)
• Locally advanced disease (i.e. surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or feasible, or easier, after cytoreduction) and/or metastatic disease
• Measurable or evaluable disease with RECIST
• Evidence of progression by RECIST during the 6 months before study entry
• Patients must be cytotoxic chemotherapy naïve (patients treated with neoadjuvant/adjuvant chemotherapy cannot be included) or could have received a previous target agent in front-line setting.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Adequate bone marrow function
• Adequate organ function
• Cardiac ejection fraction ≥50% as measured by echocardiogram
• Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study.
• No history of arterial and/or venous thromboembolic event within the previous 12 months.

You may not qualify if:

• Any prior treatment with cytotoxic chemotherapy
• \>1 line of anticancer targeted agents
• Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing
• Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered
• Previous radiotherapy to 25 % of the bone marrow
• Major surgery within 4 weeks prior to study entry
• Other primary malignancy with \<5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse
• Pregnancy or breast feeding
• Cardiovascular diseases resulting in a New York Heart Association Functional Status \>2 (24). Medical history of a myocardial infarction \< 6 months prior to initiation of study treatment
• Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment
• Known history of human immunodeficiency virus infection
• Active or chronic hepatitis B or C requiring treatment with antiviral therapy
• Medical history of hemorrhage or a bleeding event ≥ Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment
• Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs

Sponsors & Collaborators

• Italian Sarcoma Group: lead

Study Sites (6)

Nuovo Ospedale di Prato

Prato, Firenze, 59100, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

Location

IRCCS Istituto ortopedico Rizzoli

Bologna, 40136, Italy

Location

Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo -

Candiolo, 10060, Italy

Location

Ospedale Giaccone

Palermo, Italy

Location

Related Publications (12)

• Dagrada GP, Spagnuolo RD, Mauro V, Tamborini E, Cesana L, Gronchi A, Stacchiotti S, Pierotti MA, Negri T, Pilotti S. Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation. Mod Pathol. 2015 Aug;28(8):1074-83. doi: 10.1038/modpathol.2015.70. Epub 2015 May 29.

  PMID: 26022454 BACKGROUND

• Beadle GF, Hillcoat BL. Treatment of advanced malignant hemangiopericytoma with combination adriamycin and DTIC: a report of four cases. J Surg Oncol. 1983 Mar;22(3):167-70. doi: 10.1002/jso.2930220306.

  PMID: 6682161 BACKGROUND

• Stacchiotti S, Libertini M, Negri T, Palassini E, Gronchi A, Fatigoni S, Poletti P, Vincenzi B, Dei Tos AP, Mariani L, Pilotti S, Casali PG. Response to chemotherapy of solitary fibrous tumour: a retrospective study. Eur J Cancer. 2013 Jul;49(10):2376-83. doi: 10.1016/j.ejca.2013.03.017. Epub 2013 Apr 6.

  PMID: 23566418 BACKGROUND

• Stacchiotti S, Tortoreto M, Bozzi F, Tamborini E, Morosi C, Messina A, Libertini M, Palassini E, Cominetti D, Negri T, Gronchi A, Pilotti S, Zaffaroni N, Casali PG. Dacarbazine in solitary fibrous tumor: a case series analysis and preclinical evidence vis-a-vis temozolomide and antiangiogenics. Clin Cancer Res. 2013 Sep 15;19(18):5192-201. doi: 10.1158/1078-0432.CCR-13-0776. Epub 2013 Jul 25.

  PMID: 23888069 BACKGROUND

• Park MS, Ravi V, Conley A, Patel SR, Trent JC, Lev DC, Lazar AJ, Wang WL, Benjamin RS, Araujo DM. The role of chemotherapy in advanced solitary fibrous tumors: a retrospective analysis. Clin Sarcoma Res. 2013 May 11;3(1):7. doi: 10.1186/2045-3329-3-7.

  PMID: 23663788 BACKGROUND

• Chaigneau L, Kalbacher E, Thiery-Vuillemin A, Fagnoni-Legat C, Isambert N, Aherfi L, Pauchot J, Delroeux D, Servagi-Vernat S, Mansi L, Pivot X. Efficacy of trabectedin in metastatic solitary fibrous tumor. Rare Tumors. 2011 Jul 11;3(3):e29. doi: 10.4081/rt.2011.e29. Epub 2011 Jul 18.

  PMID: 22066036 BACKGROUND

• Khalifa J, Ouali M, Chaltiel L, Le Guellec S, Le Cesne A, Blay JY, Cousin P, Chaigneau L, Bompas E, Piperno-Neumann S, Bui-Nguyen B, Rios M, Delord JP, Penel N, Chevreau C. Efficacy of trabectedin in malignant solitary fibrous tumors: a retrospective analysis from the French Sarcoma Group. BMC Cancer. 2015 Oct 15;15:700. doi: 10.1186/s12885-015-1697-8.

  PMID: 26472661 BACKGROUND

• Domont J, Massard C, Lassau N, Armand JP, Le Cesne A, Soria JC. Hemangiopericytoma and antiangiogenic therapy: clinical benefit of antiangiogenic therapy (sorafenib and sunitinib) in relapsed malignant haemangioperyctoma /solitary fibrous tumour. Invest New Drugs. 2010 Apr;28(2):199-202. doi: 10.1007/s10637-009-9249-1. Epub 2009 Apr 8. No abstract available.

  PMID: 19352594 BACKGROUND

• Park MS, Patel SR, Ludwig JA, Trent JC, Conrad CA, Lazar AJ, Wang WL, Boonsirikamchai P, Choi H, Wang X, Benjamin RS, Araujo DM. Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor. Cancer. 2011 Nov 1;117(21):4939-47. doi: 10.1002/cncr.26098. Epub 2011 Apr 8.

  PMID: 21480200 BACKGROUND

• Valentin T, Fournier C, Penel N, Bompas E, Chaigneau L, Isambert N, Chevreau C. Sorafenib in patients with progressive malignant solitary fibrous tumors: a subgroup analysis from a phase II study of the French Sarcoma Group (GSF/GETO). Invest New Drugs. 2013 Dec;31(6):1626-7. doi: 10.1007/s10637-013-0023-z. Epub 2013 Sep 5.

  PMID: 24005614 BACKGROUND

• Stacchiotti S, Tortoreto M, Baldi GG, Grignani G, Toss A, Badalamenti G, Cominetti D, Morosi C, Dei Tos AP, Festinese F, Fumagalli E, Provenzano S, Gronchi A, Pennacchioli E, Negri T, Dagrada GP, Spagnuolo RD, Pilotti S, Casali PG, Zaffaroni N. Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour. Eur J Cancer. 2014 Nov;50(17):3021-8. doi: 10.1016/j.ejca.2014.09.004. Epub 2014 Sep 27.

  PMID: 25269954 BACKGROUND

• Martin-Broto J, Pousa AL, de Las Penas R, Garcia Del Muro X, Gutierrez A, Martinez-Trufero J, Cruz J, Alvarez R, Cubedo R, Redondo A, Maurel J, Carrasco JA, Lopez-Martin JA, Sala A, Meana JA, Ramos R, Martinez-Serra J, Lopez-Guerrero JA, Sevilla I, Balana C, Vaz A, De Juan A, Alemany R, Poveda A. Randomized Phase II Study of Trabectedin and Doxorubicin Compared With Doxorubicin Alone as First-Line Treatment in Patients With Advanced Soft Tissue Sarcomas: A Spanish Group for Research on Sarcoma Study. J Clin Oncol. 2016 Jul 1;34(19):2294-302. doi: 10.1200/JCO.2015.65.3329. Epub 2016 May 16.

  PMID: 27185843 BACKGROUND

MeSH Terms

Conditions

Solitary Fibrous Tumors

Interventions

Trabectedin; Doxorubicin; Dacarbazine

Condition Hierarchy (Ancestors)

Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Triazenes; Imidazoles; Azoles

Study Officials

• Silvia Stacchiotti, MD

  Italian Sarcoma Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: January 18, 2017
• Study Start: March 4, 2018
• Primary Completion: December 6, 2024
• Study Completion: December 6, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)